Abstract: The invention in the field of cell biology relates to novel peptides able to interact with intracellular signal transducers, thus interfering with signal transduction pathways leading to cell proliferation and motility. The peptides of the invention may be chemically synthesized from single amino acids and/or preformed peptides of two or more amino acid residues.The peptides of the invention find an useful application in the treatment of a neoplastic disease.

Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. Plate embodiments include substrates of physically bonded (e.g.

Abstract: Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on or in its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. The preferred plate embodiment employs an HPMP wink of porous polyolefin removably received in holes in the plate. A unique multi-slot block assembly is used to prepare the ASPCLs.

Abstract: Polypeptides, sets and libraries of sets of polypeptides that are related in sequence to the polypeptide of SEQ ID NO:1 are disclosed that have antimicrobial, hemolytic and hydrolytically catalytic activities, as are processes for making and using the same. A contemplated set is a mixture of equimolar amounts of a polypeptide of SEQ ID NO:2. Particularly preferred polypeptides include those of SEQ ID NOs:3-9.

Abstract: Peptides which include unnatural amino acids and which either promote or inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.

Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.

Abstract: Peptides which bind to selected ligands are identified by screening peptide libraries which encode a random or controlled collection of amino acid sequences. A rapid and convenient iterative strategy is employed to determine the peptide sequences which bind to the ligand of interest. The peptides so identified can be used as diagnostic or therapeutic agents, or in the design of lead compounds for such uses.

Abstract: Synthetic peptide combinatorial libraries (sets) having a single, predetermined amino acid residue at a single, predetermined oligopeptide chain position and mixtures of amino acid residues at the other chain positions are disclosed, as are their processes of synthesis and use in determining the amino acid residue sequence of an oligopeptide ligand that binds to an acceptor molecule.

Abstract: Disclosed herein are surface activated, organic polymers useful for biopolymer synthesis. Most preferably, aminated biaxially oriented polypropylene is used for the synthesis of oligonucleotides thereto, and these devices are most preferably utilized for genetic analysis of patient samples.

Abstract: A method for cyclization and reversal of the polarity of polymers on a substrate. The method provides for the formation of a polymer on a substrate (2) with a tether molecule (4). Through unmasking of a protective group (PG.sub.2) a cyclic polymer (6) is formed. Through cleavage of an appropriate bond, a polarity reversed polymer (8) is formed. The method finds particular application in the formation of, for example, peptides and oligonucleotides.

Abstract: The present invention pertains to polyethylene glycol (PEG) derivatized graft supports, to methods for making these supports and to methods of using the supports to synthesize peptides by solid-phase synthesis techniques. The PEG-graft supports of this invention comprise functionalized PEG derivatives which are covalently attached to solid supports, such as polystyrene.

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: A method for incorporating novel phosphine containing amino acids into peptide sequences is provided. The resulting phosphine-containing peptides can be used to bind a transition metal between two phosphine moieties presented on an amino acid in a peptide. The resulting phosphine-containing peptide metal complex is useful as a stereoselective catalyst of a chemical reaction or as a means for delivering a metal selectively to a target tissue or organ for medical uses.

Abstract: Apparatus and method for the automated synthesis of DNA segments utilizing multiple reaction columns, all of which are open at the inlet end to the atmosphere of a reaction chamber. A movable reagent supply line outlet is positioned adjacent to the column inlet end to apply reagent to each of the columns according to an input sequence of delivery. The delivery sequence is under processor control. Reagents are removed from all columns simultaneously through the application of vacuum at the outlet end of each column. The device enables the parallel synthesis of large numbers of different oligonucleotide sequences of different lengths.

Abstract: A method for sequencing proteins on a polytetrafluoroethylene support is described. The support is preferably porous. The sample to be sequenced may be transferred directly, e.g., by blotting, to the support. Covalent binding of the sample to the support is not required.

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 method of making random libraries of peptide nucleic acids using the fully preformed monomers.

Abstract: A method for correlating a peptide fragment mass spectrum with amino acid sequences derived from a database is provided. A peptide is analyzed by a tandem mass spectrometer to yield a peptide fragment mass spectrum. A protein sequence database or a nucleotide sequence database is used to predict one or more fragment spectra for comparison with the experimentally-derived fragment spectrum. In one embodiment, sub-sequences of the sequences found on the database which define a peptide having a mass substantially equal to the mass of the peptide analyzed by the tandem mass spectrometer are identified as candidate sequences. For each candidate sequence, a plurality of fragments of the sequence are identified and the masses and m/z ratios of the fragments are predicted and used to form a predicted mass spectrum.

Abstract: A method for the separation of at least one specific binding entity from a mixture of binding entities, which comprises the steps of contacting said mixture of binding entities with an immobilized peptide in which said peptide specifically binds to said specific binding entity, and separating the immoblized peptide/specific binding entity complex from the mixture of binding entities; an immobilized peptide-solid support preparation comprising a cleavable link between the peptide and the solid support, and a method for the preparation of a peptide from an immobilized peptide-solid support preparation.

Abstract: The present invention provides methods and reagents for sequencing amino acids. One embodiment of the method for determining the terminal amino acid of a polypeptide comprises the steps of (a) attaching (either covalently or non-covalently) the polypeptide to a solid support, (b) reacting the polypeptide with a compound described below, under conditions and for a time sufficient for coupling to occur between the terminal amino acid of the polypeptide and the compound, thereby yielding a polypeptide with a derivatized terminal amino acid, (c) washing the solid support to remove unbound material, (d) cleaving the derivatized terminal amino acid from the polypeptide with a cleaving agent, (e) ionizing the cleaved derivatized terminal amino acid, and (f) determining the molecular weight of the derivatized terminal amino acid, such that the terminal amino acid is determined.Within one embodiment, the compound is p-isothiocyanato phenethyl trimethylammonium and counterion salts thereof.

Abstract: A procedure for the preparation of salmon calcitonin comprising the condensation of fragment 1(SEQ ID NO: 1), a docosapeptide corresponding to the carboxamide end of the salmon calcitonin sequence conveniently protected and anchored on resin, with fragment 2(SEQ ID NO:2), a decapeptide corresponding to the amino end of the salmon calcitonin sequence conveniently protected and with a disulphide bridge ready formed between the two cysteines, and the treatment of the complete peptide skeleton (fragment 6 (SEQ ID NO:6)) with an acid to liberate the totally deprotected peptide from the resin.

Abstract: A protein or peptide is treated by a vapor containing an organic acid represented by the following general formula CF.sub.3 --(CF.sub.2)n--COOH (n is zero or more integer). The resulting reaction mixture is processed by a mass spectrometer to obtain a mass spectrum to measure a mass of respective chemical species contained in the reaction mixture. Alternatively, the reaction mixture is processed by an amino acid analyzer to determine an amino acid sequence of the protein or peptide from the carboxy-terminal. According to another method, the protein or peptide is treated by an anhydride of the organic acid represented by the following general formula CF.sub.3 --(CF.sub.2)n--COOH (n is zero or more integer). The resulting reaction mixture is processed by a mass spectrometer to obtain a mass spectrum to measure a mass of respective chemical species contained in the reaction mixture to determine an amino acid sequence of the protein or peptide from the carboxy-terminal.

Abstract: Polymer-bound mixed carboxylic anhydrides can be prepared under mild conditions by the condensation of carboxylic acids (including N-protected amino acids) with polymer-bound acid chlorides. These mixed anhydrides function as polymeric reagents in the sense that they will react readily with monomeric nucleophiles such as amines to form amide or peptide products, depending on the identities of the mixed anhydride and amine reactants. However, in spite of their reactivity, these polymeric mixed anhydrides exhibit a significant degree of stability under conditions of prolonged storage, which suggests that such compounds have commercial utility as a relatively stable form of highly activated carboxylic acids. The polymeric support can be reactivated and recycled for repeated use in the derivatization process.

Abstract: A large pore polyamide resin is useful for large peptide and protein (protide) synthesis. A method of preparing the same comprises mixing a dimethylacrylamide monomer with an unsaturated or alkenoyl amine monomer, a cross-linker and water, homogeneously emulsifying the aqueous mixture with an organic solvent in the presence of an emulsifier, adjusting the pH of the aqueous mixture during polymerization to 6-8.5 to produce large pore resin beads, and isolating the beads. The beads may be used as a solid phase substrate for the synthesis of a polyamide/protide conjugate. The polyamide resin/protide conjugate may be used, without separation of the protide from the resin or subsequent purification, for immunizing mammals, including humans, against the protide, for affinity purifying immunological molecules binding to the protide, and for immunoassays.

Abstract: A process for the solid phase synthesis of peptides containing an aza-amino acid, for example the decapeptide goserelin, which comprises:(i) assembling all the amino acids of the peptide except the C-terminal aza-amino acid by conventional solid phase synthesis;(ii) cleaving the peptide from the support with hydrazine or a substituted hydrazine; and(iii) reacting the hydrazide thus released with a cyanate ion.

Abstract: A peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 43); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide). The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: The invention concerns peptides which have a partial sequence of lipoprotein (a) as well as their use for the purification of antibodies by means of affinity chromatography, as an immunogen for the production of antibodies and as a standard in an immunological test or as a competitive hapten in an agglutination test.

Abstract: The present invention relates to a method for peptide C-terminal fragment sequence analysis, in which the fragment collection is carried out on an allylamine group-derivatized polymer membrane or on allylamine group-derivatized glass fiber filter paper; the collected C-terminal fragment is immobilized thereon using a water-soluble carbodiimide etc.; and the obtained immobilized product is subjected directly to amino acid sequence analysis. The present invention also relates to an apparatus for collecting a peptide fragment. According to the method of the present invention, peptides which are rich in hydrophobic groups in their C-terminus and are therefore difficult to trap with polyvalent ion carriers, currently used in the gas-phase sequencer, can be completely analyzed up to their C-terminus. Also, amino acid sequence analysis can be made even when the amount of C-terminal fragments is very small.

Abstract: Described are derivatives of the precursor peptide of the cardiodilatin/atrial sodiuretic factor (CDD-ANF) or fragments thereof which comprise at least the amino acid sequence of alpha-hANaP. The derivatives according to the present invention are compounds of the formula (I) ##STR1## X is a phosphate or thiophosphate group. R is NH.sub.2 or a peptide fragment from the amino acid sequence of gamma-hANaP. Radio-labelled derivatives are also possible. A method for the qualitative and/or quantitative determination of peptides containing the sequence of alpha-hANaP and a use of the compounds having the formula (I) as medicaments for various vaso- and renal related disorders are further described.

Abstract: Compounds of formula I are described, ##STR1## wherein n is equal to one or two, R.sub.1 stands for hydrogen or an amino protecting group, R.sub.2 represents hydrogen or a carboxyl protecting group and R.sub.3 4-methyltriphenylmethyl, 4,4'-dimethyltriphenylmethyl, 4,4',4"-trimethyltriphenylmethyl. Furthermore described are compounds of formula I which are reactive and suitable for coupling reactions and are derived from I with R.sub.2 =H by activation of the carboxyl group.The compounds mentioned above can be used as starting materials for the synthesis of peptides. They are more suitable than analogous compounds of formula I, wherein R.sub.3 represents hydrogen or a carbamoyl protecting group used hitherto.

Abstract: The invention provides methods and apparatuses for solid-phase peptide synthesis which employ solvent/reagent delivery and measuring systems open to atmospheric pressure coupled to pressurized transfer and reaction systems. The delivery and measuring systems consists of multiple solvent vessels connected to a metering vessel through individual, uninterrupted solvent lines. The metering vessel is connected to a transfer vessel by a valve through which solvent is gravity fed to the transfer vessel. The solvent is now in a closed, single pathway system and can be pressurized from the transfer vessel to a reaction vessel. This closed system allows the complete inversion of the reaction vessel; with the advantage of guaranteeing complete resin to solvent contact without any possibility of loss of resin product.

Abstract: Ink-jet printing technology is applied to the creation of multi unit chemical compound libraries. Ink-jet type nozzles are used to inject multiple droplets onto the surface an appropriate support, such droplets consisting of solutions containing units of the chemical compound that will attach to the support surface. Droplets are then injected, by such nozzles, onto the support attached unit droplets that contain units that will attach to such support attached units. The second step is repeated to create multiple varying unit chemical compounds. Ink-jet printing technology allows the deposition of small droplets that do not overlap or splatter. The system is particularly useful in the creation of libraries of multiple peptide compounds where the units are amino acids.

Abstract: Peptides immunoreactive with antibodies to native proteins, and which have at least two cysteine residues that contribute to mimicking an epitope of the protein, are prepared with the cysteine thiol groups protected. When deprotected, the peptides have enhanced immunoreactivity. The peptides are particularly useful for detecting antibodies or antigens associated with retroviruses, including the clinically important lymphotropic retroviruses HIV-1, HIV-2, HTLV-I, and HTLV-II.

Abstract: A method to obtain selected individual peptides or families thereof which have a target property and optionally to determine the amino acid sequence of a selected peptide or peptides to permit synthesis in practical quantities is disclosed. In general outline, the method of the invention comprises synthesizing a mixture of randomly or deliberately generated peptides using standard synthesis techniques, but adjusting the individual concentrations of the components of a mixture of sequentially added amino acids according to the coupling constants for each amino acid/amino acid coupling. The subgroup of peptides having the target property can then be selected, and either each peptide isolated and sequenced, or analysis performed on the mixture to permit its composition to be reproduced. Also included in the invention is an efficient method to determine the relevant coupling constants.

Abstract: In this invention, a peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 47); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide).The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: Processes for synthesizing polypeptides containing substantially non-antigenic polymers, preferably poly(alkylene glycols) in specifically predetermined sites are disclosed. Polypeptides prepared by such processes acre also disclosed.

Abstract: A method is disclosed for the rapid synthesis of very large numbers of peptides which can be integrated with the screening of these peptides as heterogeneous mixtures to identify the specific peptides which demonstrate biological activity using a small number of coupling steps.

Abstract: A method to obtain selected individual peptides or families thereof which have a target property and optionally to determine the amino acid sequence of a selected peptide or peptides to permit synthesis in practical quantities is disclosed. In general outline, the method of the invention comprises synthesizing a mixture of randomly or deliberately generated peptides using standard synthesis techniques, but adjusting the individual concentrations of the components of a mixture of sequentially added amino acids according to the coupling constants for each amino acid/amino acid coupling. The subgroup of peptides having the target property can then be selected, and either each peptide isolated and sequenced, or analysis performed on the mixture to permit its composition to be reproduced. Also included in the invention is an efficient method to determine the relevant coupling constants.

Abstract: A solid phase coupling reagent for amide formation, comprising insoluble polymer bearing pendant side chains, said side chains each comprising a terminal portion having the formula ##STR1## wherein Y.sup.- is a counteranion and n is independently an integer from 2 to 6; and a method of making amides employing the coupling reagent.

Abstract: A technique for the synthesis of arrays of diverse polymers such as polypeptides and nucleic acids. The technique beneficially utilizes solid-phase chemistry techniques. Preferred embodiments utilize photolabile protecting groups, and photolithography. The technique forms polymers with monomer sequences and locations determined by the order of addition of monomers and the activation patterns formed on the substrate.

Abstract: Disclosed are proteins derived from the sand fly Lutzomyia longipalpis capable of inducing vasodilation in mammals, and data characterizing the proteins and nucleic acid encoding the proteins. Also disclosed is a method for temporarily inactivating the immune system in a mammal comprising administering to the mammal the Lutzomyia protein, CGRP, calcitonin, or active immune suppressing analogs thereof.

Abstract: This invention relates to a biotinylating reagent being used in purification process for synthesis mature peptide. The reagent has at one terminus a functional group capable of forming a bond with the N-terminus amino group of the mature peptide. The bond is stable to the final deprotection reaction under acidic condition at the post-synthesis step of the peptide synthesis process while the bond is specifically cleaved under a difined condition such as basic condition. The reagent also has at the other terminus a biotinyl group. The biotinyl-avidin coupling is used when the reagent modified mature peptide are immobilized selectively on avidin-agarose column. The compounds having following formula (II) are preferable as the reagent.

Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Abstract: Solid-phase peptide synthesis is performed with solvent/reagent delivery and measuring systems open to atmospheric pressure coupled to pressurized transfer and reaction systems. The delivery and measuring systems consists of multiple solvent vessels connected to a metering vessel through individual, uninterrupted solvent lines. The metering vessel is connected to a transfer vessel by a valve through which solvent is gravity fed to the transfer vessel. The solvent is now in a closed, single pathway system and can be pressurized from the transfer vessel to a reaction vessel. This closed system allows the complete inversion of the reaction vessel; with the advantage of guaranteeing complete resin to solvent contact without any possibility of loss of resin product. All of the steps are accomplished by the opening and closing of individual valves that are controlled through a personal computer and system software that allow the user to do these steps individually or in any combination and length.

Abstract: A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion.

Abstract: There are described a device and method for doing confined reactions such as PCR amplification and detection, wherein solids (e.g., beads) used to obtain separation between bound and "free" label reagents, are transferred from region to region, specifically through a wash liquid so as to wash off the "free" label reagent from the solids. Separate chambers have dividers that are overcome by piercing or by liquification, to create passageways for the transfer of the solids. The passageways remain contained within the device.

Abstract: A compound of the formula ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting group or hydrogenAA is an amino acid residue andX is H or a protecting group useful as a coupling agent in peptide synthesis.

Abstract: The invention relates to a process for the preparation of an oligopeptide or amino acid alkyl ester.HCl salt, the alkyl group being methyl, ethyl, isopropyl or n-propyl, by converting an oligopeptide.HCl salt or amino acid.HCl salt with an alkanol corresponding to the alkyl group under the influence of an acid catalyst, 0.01-0.5 mol HCl relative to the oligopeptide.HCl salt or amino acid.HCl salt in combination with an acid ion exchange resin being used as acid catalyst.

Abstract: An apparatus is disclosed for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier comprises a planar porous material divided into functionalized compartments, into which an active component is put, via a dispensing head.

Abstract: A method is disclosed for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier is a planar porous material divided into functionalized compartments, into which an active component is put, via a dispensing head.

Abstract: Proteins which specifically inhibit coagulation Factor Xa. The inhibitors, which do not inhibit Factor VIIa, kallikrein, trypsin, chymotrypsin, thrombin, urokinase, tissue plasminogen activator, plasmin, elastase, Factor XIa or S. aureus V8 protease, are polypeptides of 60 amino acid residues. The inhibitors may be purified from Ornithodoros moubata extract, synthesized, or produced using a recombinant DNA yeast expression system.