Abstract: The invention concerns libraries of chemical compounds, that are useful in medicinal chemistry and related arts, their methods of manufacture and methods of their use. In one embodiment the individual chemical species of the library are synthesized aleatoricly, i.e, by a process involving chance. The chemical species of the library are used while attached to solid phase supports. The library differs from previously disclosed libraries that were intended to be screened while in solid phase in that each individual solid phase support or identifiable portion of a solid phase array displays many species of ligands, collectively termed a "set." The library is constructed so that each set contains a single invariant structure, common to all the species of ligands attached to the particular solid phase support, which is termed a "motif." The invention teaches that libraries of motifs can be employed advantageously compared to known libraries wherein a single species is present on each support.

Abstract: The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon-carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided.

Abstract: A technique for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

Abstract: The present invention is directed to a novel "handle" for solid phase peptide synthesis. The handles can be converted from a stable form to a labile form, allowing for cleavage of a peptide amide from the support after synthesis under mild conditions, and after deprotection of the amino acid side chains. The handles are based on a substituted benzhydrylamine skeleton.

Abstract: The present invention is directed to linkers based on ester bond linkages, especially iminodiacetic acid ester bond linkages, for use in solid phase peptide synthesis. In particular, the invention is directed to cleavable linkers that can release peptide from the solid phase support under relatively mild conditions by formation of a diketopiperazine or other cyclic structure, such that the cyclic structure remains on the solid phase support, and, in a second cleavage, under more stringent conditions of high pH. The invention is further directed to solid phase supports prepared with multiple cleavable linkers, including a linker that is cleaved by formation of a cyclic product. One such second linker is an ester of hydroxymethylbenzoic acid, or esters formed by carboxy groups of aspartic or glutamic acid.

Abstract: A solid phase synthesis system is provided by employing a fully automated robot that operates with a novel timing protocol for handling multiple synthetic tasks efficiently. The novel timing protocol is realized by performing steps in the synthesis cycles for different compounds, such as peptides, concurrently rather than on a sequential basis.

Abstract: Analogues of 8-D-homoarginine vasopressin were prepared with the general formula ##STR1## where X is L-O-methyltyrosine, L-p-ethylphenylalanine, D-p-ethylphenylalanine, L-p-methylphenylalanine or D-methylphenylalanine and R is cysteine or .beta.-mercaptopropionic acid. These vasopressin analogues exhibited an increased affinity to uterus receptors for oxytocin, where they acted as ocytocin antagonists. Moreover, the analogues of deamino vasopressin have a significantly reduced antidiuretic activity in comparison with [8-D-arginine]vasopressin.

Abstract: The present invention relates to methods for determining the amino acid composition, and more preferably the sequence, of a peptide using mass spectrometric techniques. The method is particularly useful for sequencing peptides isolated from natural sources or from libraries of peptides that have been prepared synthetically, and for peptides that are not amenable to Edman degradation sequencing. In one embodiment, the method for determining the amino acid composition or sequence of a peptide comprises determining the difference of the mass of the peptide from the mass of a deuterium-hydrogen exchanged peptide, and from this difference determining the number of exchangeable (labile) hydrogen atoms (protons). Candidate peptides having amino acid compositions or sequences that do not contain the observed number of exchangeable protons are eliminated.

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: The invention relates to a method and apparatus 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 planar functionalized porous material divided into compartments, into which the needed activated component is put. Common operations of the synthesis are carried out by all compartments of the carrier at the same time.

Abstract: Analogs of neurohypophysial hormones with inhibition properties are described. The hormones are of the formula ##STR1## wherein in all chiral amino acids are of the L-series and the aromatic amino acid in the position 2, indicated with an asterisk, is of the D-series, and where R.sup.1 and R.sup.2 are hydrogen or a methyl group, R.sup.3 is hydrogen, an amino group, or a triglycylamine grouping, R.sup.4 is hydrogen, a methyl, ethyl or ethoxy group, R.sup.5 is S--CH.sub.2 or S--S group, X.sup.1 is a residue of isoleucine or phenylalanine, X.sup.2 is a residue of leucine or lysine, and X.sup.3 is a glycinamide residue or a hydroxyl group.These compounds exhibit inhibition effects towards the uterotonic and pressor activity of natural hormones. The common structural feature of all these analogues is the presence of an aromatic hydrophobic D-amino acid in the position 2.