Abstract: A method for the preparation of a chemical library, which method comprises synthesizing the library on a plurality of individually coded synthesis particles and wherein the particles are tracked during library synthesis under the control of robotic apparatus.

Abstract: A low monomer 1:1-monoadduct from a diisocyanate and a hydroxy(meth)acrylate with a free diisocyanate content of less than 0.7% by weight and a free NCO content of 10.4-16.4% by weight can be used as a starting material for an acrylic or NCO functionalized crosslinker; a bonding agent for coatings and adhesives; and a linker for solid-phase synthesis of oligo-nucleotides, polynucleotides or peptides. The monoadduct is obtained by converting 5-20 mol diisocyanate with 1 mol hydroxy(meth)acrylate at a temperature of 40-120 ° C. in the presence of at least one inhibitor; subsequently separating a non-converted diisocyanate from a reaction product by short-path distillation at 80-220 ° C./0.1-10 mbar; feeding air, nitrogen monoxide or oxygen or a mixture containing (a) air, oxygen or nitrogen monoxide and (b) a proportion of 1-90% by volume of carbon dioxide, nitrogen, an inert gas or a mixture thereof through a reaction apparatus.

Abstract: The synthesis of arrays of DNA probes sequences, polypeptides, and the like is carried out using a patterning process on an active surface of a substrate. An image is projected onto the active surface of the substrate utilizing an image former that includes a light source that provides light to a micromirror device comprising an array of electronically addressable micromirrors, each of which can be selectively tilted between one of at least two positions. Projection optics receives the light reflected from the micromirrors along an optical axis and precisely images the micromirrors onto the active surface of the substrate, which may be used to activate the surface of the substrate. The first level of bases may then be applied to the substrate, followed by development steps, and subsequent exposure of the substrate utilizing a different pattern of micromirrors, with further repeats until the elements of a two dimensional array on the substrate surface have an appropriate base bound thereto.

Abstract: Methods for the synthesis of &agr;-hydroxy-&bgr;-amino acid and amide derivatives and &agr;-ketoamide derivatives and novel derivatives made by these methods are provided. These methods involve reacting a N-terminally blocked (protected) aminoaldehyde with an isonitrile and a carboxylic acid to give an amino-&agr;-acyloxy carboxamide. The acyloxy group may be removed to give the derivative. Alternatively the protecting group is removed and acyl shift occurs to give the derivative. These derivatives are useful in the synthesis of compounds such as peptidyl &agr;-ketoamides and &agr;-hydroxy-&bgr;-carboxylic acid and amide derivatives. Certain of these compounds have been reported to have activity as inhibitors of proteases, such as serine proteases and cysteine proteases.

Abstract: Mixed-bed solid phases are provided, with methods for using such solid phases to isolate target nucleic acids, such as plasmid DNA, chromosomal DNA, RNA, or nucleic acids generated by enzymatic amplification from contaminants, including proteins, lipids, cellular debris, or other nucleic acids. The mixed-bed solid phases of this invention are mixtures of at least two different solid phases, each of which has a capacity to bind to the target nucleic acid under different solution conditions, and the capacity to release the nucleic acid under similar elution conditions. By exchanging solution conditions according to the methods of this invention, one can remove contaminants from the target nucleic acid bound to the mixed-bed solid phase, then elute the target nucleic acid in an elution buffer.

Abstract: Method for preparing a combinatorial chemistry library of compounds of the formula R1—C(═O)—NH—R2, wherein R1 and R2 are as defined in the specification, which comprises acylating a combinatorial chemistry intermediate of the formula 1A wherein Y1, Y2, X, n, R1 and R2 are as defined in the specification to produce a compound of the formula wherein Y1, R1, R2 and X are as defined in the specification, followed by acidolytic cleavage of the resin bound linker to release the compound of the formula R1—C(═O)—NH—R2.

Abstract: A method and library for determining the sequence of monomers in a polymer which is complementary to a receptor. The method provides for formation of pooled (6) and separate (10, 12) products. Separate products are subjected only to subsequent pooled coupling steps. Each pooled product is subsequently divided for formation of pooled and separate products. The resulting polymer library includes groups of polymer products. A first group of products (42) is used to identify the monomer at a first location in a polymer that is complementary to a receptor. A second group of products (44) is used to identify the monomer at a second location in a polymer that is complementary to a receptor.

Abstract: The present invention relates to a process of coding and identifying individual members of a chemical combinatorial library synthesized on a plurality of solid supports which undergo mix and split synthesis. The process provides for tagging the solid supports with a coding identifier that is attached to the solid support and which can be decoded by infrared or raman spectroscopy when directly attached to the support.

Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.

Abstract: The present invention relates to biologically active peptides with reduced toxicity and methods of preparing them. The peptides of the invention, which can be unsubstituted or N-terminal substituted have the formula: wherein X is a biologically active amphiphilic ion channel-forming peptide or protein, T is a lipophilic moiety or hydrogen, and W is T or hydrogen. Preferably T is: wherein R is a hydrocarbon (alkyl or aromatic or alkylaromatic) having at least 2 and no more than 10 carbon atoms. T is preferably an octanoyl group. The peptides and proteins of the invention have improved antimicrobial and anti-tumor biological activity while exhibiting reduced toxicity. A preferred method of reducing toxicity involves the formation of related methane sulfonate derivatives or analogues. Additionally, the compounds of the invention may be used to treat sepsis, septic shock, and lung infections, such as those occurring in cystic fibrosis.

Abstract: Methods and compositions are provided for producing arrays of polymeric binding agents. In the subject methods, the individual polymers of the array are synthesized using solid phase synthesis techniques on the surface of a substrate. A critical feature of the invention is that one or more locations on the substrate surface are spatially and temporally protected by a protective bubble during the synthesis protocol, where the protective bubble may be produced using any convenient bubble producing means. The bubble producing means may be a component of either a substrate or a structure separate from the substrate. Also provided are the arrays produced by the subject methods, kits for use in practicing the subject methods, and methods of using the arrays in analyte detection assays, including hybridization assays, such as gene discovery, differential gene expression and gene sequencing assays.

Abstract: A method to screen parallel combinatorial libraries for chiral selectors, for instance, a parallel library screening procedure demonstrating the chiral resolution of racemic analyte such as racemic (1-naphthyl)leucine ester. The method involves synthesis of potential chiral selectors on polymeric synthesis resins and the rapid screening of selectors directly on the resins with batch incubation, followed by circular dichroism measurement. The method does not require pre-immobilization of the analyte. The identified chiral selector is then attached onto a support and employed to resolve the racemic analyte into its R-enantiomer and S-enantiomer.

Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: Improvements in luminescence polarization assays. The improvements may include using confocal optics to increase sensitivity and accuracy, providing additional classes of tracers, providing improved methods to prepare specific luminescent tracers, and/or expanding the scope of assay targets, among others.

Abstract: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: A metallo-construct, which may be a peptide, is provided for use as a biological, therapeutic, diagnostic imaging, or radiotherapeutic agent, and for use in library or combinatorial chemistry methods. The construct has a conformationally constrained global secondary structure obtained upon complexing with a metal ion. The peptide constructs are of the general formula: R1—X—R2 where X is a plurality of amino acids and includes a complexing backbone for complexing metal ions, so that substantially all of the valences of the metal ion are satisfied upon complexation of the metal ion with X, resulting in a specific regional secondary structure forming a part of the global secondary structure; and where R1 and R2 each include from 0 to about 20 amino acids, the amino acids being selected so that upon complexing the metal ion with X at least a portion of either R1 or R2 or both have a structure forming the balance of the conformationally constrained global secondary structure.

Abstract: A scalable synthesis apparatus capable of rapid and efficient oligo synthesis. The apparatus includes a combination of dispensing elements, synthesis elements, and waste removal elements. More specifically, the synthesis elements are, in the preferred embodiment, a series of well-like synthesis locations on a continuous strip, where the strip is moving serially from one dispensing location to the next, and waste from each step is evacuated a vacuum egress element, until an entire oligo has been synthesized. Serial oligo synthesis increases the per hour productivity dramatically over batch synthesis apparatus currently used. The number of dispensing locations can be increased or decreased so that oligos of longer or shorter lengths may be synthesized. Moreover, a tremendous reduction of wasted reagents and oligo surplusage by providing serial synthesis.

Abstract: The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.

Abstract: Reaction vessels suitable for solid phase polymer synthesis generally comprise: a housing defining a chamber for containing a resin, said housing having an operable inlet port and an operable outlet port in fluid communication with said chamber; and an elongate resin filter having an interior bore, and adapted to enable filtered fluid flow from an exterior inlet surface thereof into the filter interior bore, said filter being disposed in said chamber and having an outlet connection fluidly coupling said filter interior bore to the housing outlet port such that fluid flowing through the housing inlet port into the chamber passes through the filter inlet surface, into the filter interior bore and out the housing outlet port.

Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: A method for peptide synthesis is disclosed that requires neither protecting groups nor activation of the C-&agr; carboxyl groups. The method comprises ligating a first molecule to a second molecule by promoting the orthogonal coupling of the molecules to each other. In an aspect of this method, an acyl-type reaction occurs between the molecules. The method contemplates the joining of molecules of variant size to each other, as well as the coupling of multiple identical molecules. The invention also covers the ligation of unprotected peptide, proteins or nonpeptide segments to prepare therapeutic products and synthetic vaccines with linear, circularized, or branched backbone structures, as well as the site-specific modification of peptides or proteins by lipidation and pegylation.

Abstract: Nucleic acid analogues provide a particularly useful tool for the preparation of complex polymeric structures of defined geometry because they are relatively stable to reaction conditions for the preparation of such structures and provide the opportunity to introduce reactive groups which would not be possible with usual nucleic acids. These supramolecular structures can be used to form fine networks in nanometer size, for the preparation of e.g., computer chips, new materials/polymers with conductivity and/or insulator properties, and robot arms in nanometer scale.

Abstract: Particulate labels that can be individually identified comprise particulate supports to which are bound at least two distinguishable signal generating moieties, such as fluorophores emitting at different wavelengths, which signals are detectable and measurable in situ. By varying the ratio and/or amounts of the signal generating moieties, a multiplicity of different and distinguishable labels is obtained. Each different label can then be coupled to a different reagent and the individual interactions of each reagent with a target observed in parallel.

Abstract: The present invention provides a variety of methods for synthesizing, encoding and decoding compounds in a combinatorial library. One step or cycle in the synthetic methods of the invention is a self-encoding step in which different pairs of components, each pair with a known and different molecular weight difference, are reacted with supports, whereby two compounds differing in molecular weight are formed on each support. The molecular weight difference between the two compounds on the support encodes for a particular component pair. Libraries of compounds formed according to the methods of the invention are also provided.

Abstract: The present invention provides substantially purified cryptdin peptides having a consensus amino acid sequence: X1-C-X2-C-R-X3-C-X4-E-X5-C-X6-C-C-X7 wherein X1 is 3 to 9 amino acids; X2 is one amino acid, preferably Y, H or R; X3 is 2 or 3 amino acids; X4 is three amino acids; X5 is five amino acids; X6 is 6 to 10 amino acids; and X7 is 0 to 9 amino acids.

Abstract: A method for the preparation of a fluorescence resonance energy transfer (FRET) substrate having donor and acceptor species on opposite sides of a proteolytic cleavage site and wherein the donor and/or acceptor species are attached via the side chain(s) of amino acid(s) therein. The method comprises contacting a reactive donor or acceptor species with a polypeptide substrate having the side chain(s) of amino acid(s) therein adapted for reaction with the reactive species and then contacting the substrate so obtained with a corresponding reactive donor or acceptor species. Novel FRET substrates so prepared and their use in assays to identify modulators of protease activity.

Abstract: Dimeric oligopeptide mixture sets, their synthesis and use in determining the sequence of an oligopeptide dimer ligand that optimally binds to a receptor are disclosed. A dimeric oligopeptide mixture set has two oligopeptide portions bonded together by a disulfide bond. Each oligopeptide of a first oligopeptide portion has the same number of 3 to about 10 residues including an oxidized mercaptan-containing residue that forms part of the disulfide bond and an amino acid residue sequence that includes at least one of at least six residues in addition to the oxidized mercaptan-containing residue at the same one or more predetermined positions of the oligopeptide chain. The second portion has an oligopeptide chain having a length of 4 to about 10 residues, including an oxidized mercaptan-containing residue that forms part of the disulfide bond.

Abstract: A method for extracting proteins from the intercellular space of plants is provided. The method is applicable to the large scale isolation of many active proteins of interest synthesized by plant cells. The method may be used commercially to recover recombinantly produced proteins from plant hosts thereby making the large scale use of plants as sources for recombinant protein production feasible.

Abstract: A method is provided which facilitates and enables the production of a wide range of complex conjugates composed of similar or dissimilar units linked together by amide bonds. Said method for the production of acylthio derivatives, R′—CO—SA, involves reaction of a carboxylate, R′—CO—O− (or carboxylic acid R′—CO—OH) with an iso-thiouronium derivative (bearing SA) in the presence of base. Nucleophilic counterion forms of the iso-thiouronium salts confer significant rate enhancement. The processes are simple, generally applicable, efficient, and do not require the employment of noxious reagents. The production of complex protein-like products by the intermediary of acylthio esters generated by the process of this invention, provides a method which is compatible with mild methods of chain assembly; and is preferably applied when the second component in the ligation bears an amino terminal cysteine residue.

Abstract: The present invention provides a method for producing a peptide thiol ester using fluoren-9-ylmethoxycarbonylamino acid (Fmoc-amino acid). The method is for peptide synthesis and involves (1) using and removing the Fmoc group bound as the protective group to the amino group of amino acid, fixed on a resin via the thiol ester bond, a specific reagent is used to remove an Fmoc group from the amino acid thiol ester resin; (2) adding Fmoc-amino acid to the Fmoc-freed resin and then removing the Fmoc group, repeatedly, to prepare the Fmoc-peptide thiol ester resin; and (3) treating sequentially, the Fmoc-peptide thiol ester resin with a cleavage reagent and with a reagent capable of removing the Fmoc group.

Abstract: An enzyme cleavable linker is prepared on which organic compounds are synthesized when the linker is bound to a solid phase. The linker contains a functional group on which a synthesized organic compound is bound when synthesis takes place, and a recognition site for a hydrolytic enzyme. Reacting the linker with the enzyme causes the linker to fragment at a site different from the recognition site to liberate the synthesized organic compound. The solid phase may be a crosslinked polyacrylamide containing an amino group for attaching the linker, and the linker is bound to the solid phase via a spacer. The spacer is attached to the solid phase by an ester, ether, amide or amine linkage, or a sulfide or phosphate linkage. In a specific reaction of forming a solid phase containing the linker, 2-acetoxy-5-hydroxymethylbenzoic acid is attached to an amino group-containing polymer via a spacer followed by conversion to a chloroformic ester.

Abstract: Mixed-bed solid phases are provided, with methods for using such solid phases to isolate target nucleic acids, such as plasmid DNA, chromosomal DNA, RNA, or nucleic acids generated by enzymatic amplification from contaminants, including proteins, lipids, cellular debris, or other nucleic acids. The mixed-bed solid phases of this invention are mixtures of at least two different solid phases, each of which has a capacity to bind to the target nucleic acid under different solution conditions, and the capacity to release the nucleic acid under similar elution conditions. By exchanging solution conditions according to the methods of this invention, one can remove contaminants from the target nucleic acid bound to the mixed-bed solid phase, then elute the target nucleic acid in an elution buffer.

Abstract: A method of attaching unmodified biopolymers, particularly, unmodified polynucleotides, directly to a solid support is provided. The method includes the steps of (a) providing unmodified biopolymers; (b) providing a solid support having at least one surface comprising pendant acyl fluoride functionalities, and (c) contacting the unmodified biopolymers with the solid support under a condition sufficient for allowing the attachment of the biopolymers to the solid support. The unmodified biopolymers may be nucleic acids, polypeptides, proteins, carbohydrates, lipids and analogues thereof. The unmodified polynucleotides may be DNA, RNA or synthesized oligonucleotides. The DNA may be single or double stranded. A device including a solid support and unmodified biopolymers attached to the solid support by reaction with the pendant acyl fluoride functionalities of the solid support is also provided. The methods and devices of the present invention may be used in performing hybridization assays and immunoassays.

Abstract: A synthesis member preferably comprises two elements: a crown and a stem. The stem includes a tag, such as a transponder, that is used to identify the synthesis member and/or the synthetic history of the synthesis member when used in the automated synthesis of compound libraries containing large numbers (e.g. 1000 or more) compounds. The crown provides the location at which compounds are synthesized. The combination of a crown for use with compound synthesis and stem allows the tracking of individual synthesis members from a library containing thousands of such synthesis members. Because each synthesis member is individually tracked and can be logged into a database and/or process flow control system, the synthesis of several thousand individual compounds in conventional containers, such as round bottom flasks is made possible using only traditional compound synthesis approaches.

Abstract: Compounds of the formula: X-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-  (I) Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Z wherein X is an acetyl or pyroglutamyl group and Z is —NH2, -Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-Pro-NH2, -Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-Gly-NH2, or -Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn with the proviso that when X is a pyroglutamyl group, Z is -Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn, and when X is an acetyl group, Z is other than -Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn and methods for the production thereof. The compounds are thymosin &agr;1-related compounds having uses including treatment of endotoxicity in animals.

Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Abstract: This invention features methods of biphasic synthesis for synthesizing combinatorial libraries and combinatorial libraries of chemical compounds utilizing the template, and combinatorial libraries of chemical compounds formed by the methods of this invention.

Abstract: The present invention relates to peptides and peptidomimetic compounds and pharmaceutical compositions containing them as useful pharmacological agents in the control or treatment of proliferative diseases such as cancer, against tumor growing and/or tumoral metastasis, and psoriasis and in the control or treatment of inflammatory, allergic, autoimmune, viral, and cardiovascular diseases. These new compounds have the unique property to inhibit the recognition of several phosphotyrosine containing motifs within all the cellular receptors and cytosolic transducers by a wide spectrum of SH2 domains contained in cytosolic transducers and other effector proteins laying along different pathways of the signal transduction process and with a particularly high affinity for the SH2 domain of the adaptor transducer Grb2, a key element along the pathway to mitogenesis and motogenesis, this last activity leading to invasiveness and to metastasis.

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Abstract: The preparation of 14-membered macrocycles from a resin-bound orthogonally protected lysine residue is described. Reductive alkylation of the a-nitrogen followed by acylation with an Fmoc-aminoacid provides a protected dipeptide precursor. Removal of the Fmoc-group, acylation with a succinic anhydride, methyltrityl-group removal and macrocyclization provides the desired macrocycles, after TFA cleavage, in excellent yield and purity.

Abstract: Compounds and methods are provided for diagnosing Trypanosoma cruzi infection. The disclosed compounds are polypeptides, or antibodies thereto, that contain one or more epitopes of T. cruzi antigens. The compounds are useful in a variety of immunoassays for detecting T. cruzi infection. The polypeptide compounds are further useful in vaccines and pharmaceutical compositions for inducing protective immunity against Chagas' disease in individuals exposed to T. cruzi.

Abstract: The present invention describes processes for preparing desired synthetic products that comprise a covalently bonded hydroxamic acid group —CONHOH by forming a mixture of a liquid reaction medium and a solid phase reaction product that carries a plurality of moieties of formula (A1) or (B1): where X is a residual, non-hydroxamate partial structure of the desired synthetic product, P1 is hydrogen or an amino-protecting group, P2 is hydrogen or a hydroxyl protecting group, and the bond designated (a) covalently links the moieties (A1) or (B1) to the residue of a solid substrate; by cleaving the bond designated (a) in the resultant mixture; and by separating the resultant liquid reaction phase from the resultant reaction solids to recover the desired synthetic product.

Abstract: The present invention relates to a linker shown by the following formula (I): X—SO2—R1—(A)m—R2  (I) wherein R1 is a group of the formula (A): [wherein R3, R4 and R5 are the same or different hydrogen, etc], etc, R2 is a group which can form a chemical bond to a resin which may be protected by a conventional protective group, A is lower alkylene, etc, X is a leaving group, and m is an integer of 0 or 1, with proviso that A is (C2-C6)alkylene, and m is an integer of 1, when R1 is a group of the formula (A).

Abstract: New sub-monomer synthetic methods for the preparation of peptide nucleic acid oligomeric structures are disclosed that provide for the synthesis of both predefined sequence peptide nucleic acid oligomers as well as random sequence peptide nucleic acid oligomers. Further these methods also provide for the incorporation of peptide nucleic acid units or strings of such units with amino acids or strings of amino acids in chimeric peptide nucleic acid-amino acid compounds. Further disclosed are methods of making random libraries of peptide nucleic acids using the fully preformed monomers.

Abstract: The present invention relates to a process for forming an N-&agr;-amino protected amino acid fluoride in situ by reacting an N-&agr;-amino protected amino acid with an ionic fluoride salt in the presence of a peptide coupling agent. It is also directed to the use of the amino acid fluoride thus formed in peptide synthesis.

Abstract: Linear substituted oligoalkyleneimine molecules and libraries of molecules are disclosed, as are their methods of synthesis and use in acceptor binding assays. Each molecule or chain of a library contains the same number of 2 to about 10 substituted alkyleneimine repeating units, whose substituents are reduced amino acid side chains bonded to the repeating units at a position alpha to the nitrogen atom, and the member chains of a library are present in equimolar amounts. The chains of a library contain one or more predetermined reduced amino acid side chain-substituted repeating units at one or more predetermined positions of the substituted oligoalkyleneimine chain. The library contains equimolar amounts of at least six different reduced amino acid side chain-substituted repeating units at one or more of the same predetermined positions of the substituted oligoalkyleneimine chain. Particularly preferred linear substituted oligoalkyleneimine molecules and libraries are linear substituted oligoethyleneimines.

Abstract: This invention features a template for synthesizing combinatorial libraries, methods of synthesizing combiatorial libraries of chemical compounds utilizing the template, and combinatorial libraries of chemical compounds formed by the methods of this invention.

Abstract: Cyclic penta- and hexa-peptide libraries containing one or more known amino acids, one or more randomized amino acids and a conformationally constraining element are disclosed. These peptide libraries may be used for screening for new bioactive peptides and for elucidating structural information pertinent to drug design.

Abstract: Proteins of moderate size having native peptide backbones are produced by a method of native chemical ligation. Native chemical ligation employs a chemoselective reaction of two unprotected peptide segments to produce a transient thioester-linked intermediate. The transient thioester-linked intermediate then spontaneously undergoes a rearrangement to provide the full length ligation product having a native peptide bond at the ligation site. Full length ligation products are chemically identical to proteins produced by cell free synthesis. Full length ligation products may be refolded and/or oxidized, as allowed, to form native disulfide-containing protein molecules. The technique of native chemical ligation is employable for chemically synthesizing full length proteins.

Abstract: This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: and N-oxides thereof and salts thereof.