Hoffmann-La Roche Inc.

The United States of America as Represented by the Department of Health

Johannes A Meienhofer

Arthur M Felix

David Robert Bolin

Arnold Trzeciak

Dieter Gillessen

Iou-Iou Sytwu

Edgar P Heimer

Hideo Ishitsuka

Hugo E Gallo-Torres

Su-sun Wang

Rolf Studer

Wallace M Dairman

William Lergier

Yumiko Ohta

Novel vasoactive intestinal peptide analogs containing substitutions of appropriately selected amino acids at specific positions of the VIP molecule, with potent sustained bronchodilatory activity without cardiovascular side effects.

Synthetic vasoactive intestinal peptide analogs

An improved solution phase synthesis of thymosin .alpha..sub.1 and proceeding through novel intermediates is disclosed.

Synthesis of thymosin .alpha..sub.1

An improved solution phase synthesis of thymosin .alpha..sub.1 and desacetyl thymosin .alpha..sub.1 with t-Boc side chain protection and proceeding through novel intermediates is disclosed.

Synthesis of thymosin .alpha..sub.1 and desacetyl thymosin .alpha..sub.1

Novel hexapeptides corresponding to internal fragments of thymosin .alpha..sub.1 are active as agents which restore and stimulate immune function.

Immunopotentiating peptides

Novel di-to heptapeptides representing fragments of the carboxyl terminal of thymosin .alpha..sub.1 are active as agents which affect regulation, differentiation and function of thymus dependent lymphocytes.

The present disclosure is directed to the synthesis and biological activity of [D-Thr.sup.2, .DELTA..sup.3 Pro.sup.5 ]-enkephalinamide. The subject compound is useful as an agent for the inhibition of diarrhea and also exhibits analgesic activity.

Synthesis and biological activity of [D-Thr.sup.2, .DELTA..sup.3

Novel somatostatin analogues containing one or more aminoethylglycyl residues at the amino and/or carboxyl terminus or in the ring position are described. The compounds are potent and long lasting inhibitors of gastric acid secretion.

Aminoethylglycine containing polypeptides

An improved solid phase peptide synthesis method is disclosed utilizing base labile N.alpha.-amino acid protecting groups. Such method provides a more efficient synthesis procedure in that it eliminates acid treatment thereby preventing loss of peptide from the support during each deprotection cycle and eliminates a substantial number of wash cycles in each step. A preferred base labile N.alpha.-amino protecting group is the 9-fluorenylmethyloxycarbonyl group (Fmoc) and a preferred base for deprotection is piperidine.

Solid phase synthesis with base N alpha-protecting group cleavage

Human .beta.-endorphin (.beta..sub.h -endorphin) is prepared by solution phase peptide synthesis. Synthesis proceeded via the protected .beta.-endorphin fragments 1-9, 10-18, 19-21 and 22-31.

Synthesis of human .beta.-endorphin

The use of catalytic hydrogenolysis to selectively deblock protected moieties in sulfur containing compounds has not been a practical process due to poisoning of the catalyst by the sulfur compound. It has now been found that catalytic hydrogenolysis of sulfur compounds can be successfully carried out by conducting the reaction in liquid ammonia as solvent.

Growing community of inventors

Upper Montclair, NJ, United States of America

Johannes A Meienhofer