Abstract: Novel photo-active labeled diagnostic and therapeutic peptides which are conformationally constrained backbone cyclized somatostatin analogs, having improved somatostatin receptor subtype affinity and selectivity are disclosed. The backbone cyclized peptide analogs disclosed possess unique and superior properties over other analogs, such as chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Furthermore, the unique patterns of receptor subtype selectivity provide compounds having improved diagnostic and therapeutic utilities. Pharmaceutical compositions comprising the photo-active backbone cyclized somatostatin analogs, reagents for synthesizing same, and methods of using such compositions for diagnostic and therapeutic purposes including optical imaging and photodynamic therapy are also disclosed.

Abstract: Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N?(?-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N?(?-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

Abstract: Methods of use of pharmaceutical compositions and novel peptides which are conformationally constrained backbone cyclized somatostatin analogs, having somatostatin receptor subtype selectivity, are disclosed. These patterns or receptor subtype selectivity provide compounds having improved therapeutic utility. Methods for synthesizing the somatostatin analogs and for screening of the somatostatin analogs are also disclosed. Furthermore, pharmaceutical compositions comprising somatostatin analogs are disclosed.

Abstract: A process is disclosed for using bis-(trichloromethyl)carbonate (triphosgene), diphosgene or phosgene as efficient and effective coupling reagents during coupling of carbohydrates to peptide chains. This process is particularly useful for the coupling to sterically hindered amino acid residues, or for other difficult couplings. The reagents can be used for the derivatization of peptides by formation of a bond between a free amine on a peptide and a carbohydrate.

Abstract: Novel isoquinoline derivatives which are useful as inhibitors of protein kinases for experimental, medical, and drug design purposes are disclosed. Preferred compounds which are specific inhibitors of protein kinase B are also disclosed. Furthermore, pharmaceutical compositions comprising these protein kinase inhibitors, and methods of using such compositions for treatment and diagnosis of cancers, diabetes, cardiovascular pathologies, hemorrhagic shock, obesity, inflammatory diseases, diseases of the central nervous system, and autoimmune diseases, are also disclosed.