Hoffmann-la Roche Inc.

Roche Vitamins Inc.

The United States of America

Edgar P Heimer

Arthur M Felix

Thomas F Mowles

Premkumar E Reddy

Robert C Gallo

Vincent Stewart Madison

Flossie Wong-Staal

Johannes A Meienhofer

Hugo E Gallo-Torres

David Charles Fry

Wallace M Dairman

Alexander Leopold Nussbaum

Novel growth hormone releasing factor analogs are presented having a sequence of from about twenty-nine (29) to about forty-four (44) amino acids (SEQ ID NO: 6) wherein Xaa at position 1 is His, 3-MeHis, desNH.sub.2 His, Tyr, or desNH.sub.2 Tyr; Xaa at position 2 is Val, Leu, lie, Ala, D-Ala, N-Methyl-D-Ala, Gly, NIe, or Nval; Xaa at position 8 is Gln, Ser, or Thr; Xaa at position 15 is Ala or Leu; Xaa at position 27 is Met, Nle or Leu; Xaa at position 28 is Ser or Asn; Xaa at position 29 is an amino acid residue sequence (SEQ ID NO: 7) or fragments thereof where the fragment is reduced in number by one to fifteen amino acid residues from the carboxyl-terminus, where the carboxyl terminus can be the free carboxylic acid or the corresponding amide, and the pharmaceutically acceptable acid or base addition salts thereof. The novel growth hormone releasing factor analogs demonstrate enhanced potency for the release of growth hormone, have enhanced enzymatic stability, improved half-life stability in aqueous solution, and can be administered to a subject having a deficiency of growth hormone or for improvement of growth performance in livestock and other warm blooded animals and in fish and other cold blooded marine animals.

Growth hormone releasing factor analogs

Novel growth hormone releasing factor analogs are presented having the formula: ##STR1## wherein R.sub.1 is His, 3-MeHis, desNH.sub.2 His, Tyr, or desNH.sub.2 Tyr; R.sub.2 is Val, Leu, or Ile; R.sub.3 is Ala; R.sub.4 is Met, Leu, Ile, or Nle; R.sub.5 is Ser or Asn; R.sub.6 is an amino acid residue sequence selected from Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu or fragments thereof where the fragment is reduced in number by one to fifteen amino acid residues from the amino acid residue which carries the substituent X; and X is either OH or NH.sub.2, and the pharmaceutically acceptable acid or base addition salts thereof. The novel growth hormone releasing factor analogs demonstrate enhanced potency for the released growth hormone, have enhanced enzymatic stability, and can be administered to a subject having a deficiency of growth hormone or for improvement of growth performance in livestock.

Histidine substituted growth hormone releasing factor analogs

GRF(1-44)-NH.sub.2 is prepared by the trypsin catalyzed enzymatic coupling of Leu-NH.sub.2 to GRF(1-43)-OH. The latter compound may be obtained by recombinant DNA synthesis. Thus the present method provides an economical pathway to the clinically important GRF(1-44)-NH.sub.2 compound.

Process for the enzymatic preparation of GRF(1-44)NH.sub.2

Linear and cyclic Growth Hormone Releasing Factor Analogs and a method for stimulating the release of Growth Hormone in subjects by administering to the subject an effective amount of the compounds of the invention.

Cyclic growth hormone releasing factor analogs and method for the

Synthetic peptides containing the epitopic sequence HTLV env (578-608) are useful as reagents in immunoassays for detection of AIDS antibodies, as immunogens for eliciting polyclonal or monoclonal antibodies against AIDS virus env protein and as components in an AIDS vaccine.

HTLV-III (LAV) envelope peptides

The present disclosure relates to synthetic peptides derived from the conserved region of the HTLVIII envelope proteins. These peptides are useful as reagents for immunoassays for detection of AIDS antibodies, as components of immunogenic compositions useful as vaccines, and for the production of anti-bodies selective to said envelope protein and methods for detecting the presence of AIDS antibodies in biological fluid samples.

HTLV-III envelope peptides

The invention is directed to analogs of GRF or fragments thereof wherein the fragment is reduced in number by one to fifteen amino acids from the carboxyl end wherein the analogs have the formula: ##STR1## wherein R is desNH.sub.2 -Tyr, Tyr, D-Tyr, Ac-Tyr, His or C.sup..alpha. -Methyl-Tyr; R.sub.1 is Ala, N-Methyl-D-Ala or D-Ala; R.sub.2 is Lys, Ala, Leu, Val or Ile; R.sub.3 is Ala, Leu, Val, Ile, Nle, Nval, .beta.-Ala or .alpha.-Aib; R.sub.4 is Lys, Ala, Leu, Val or Ile; R.sub.5 is Met, Leu, Nle or Ile; R.sub.6 is Asn or Ser; X is hydrogen or --COR.sub.7 ; R.sub.7 is hydrogen, C.sub.1-4 alkyl or halo(C.sub.1-4)alkyl; Y is --OR.sub.8 or --NR.sub.9 R.sub.10 ; R.sub.8 is hydrogen or C.sub.1-5 -alkyl; R.sub.9 and R.sub.10 independently equal hydrogen, C.sub.1-7 alkyl, C.sub.2-4 alkenyl or halo(C.sub.1-4)alkyl; and pharmaceutically acceptable acid or base addition salts thereof. The invention is further directed to pharmaceutical compositions and to methods for treating growth hormone deficiencies.

Polypeptides corresponding to growth hormone releasing factor in which methionine at position 27 has been replaced by a leucine residue retain full growth hormone releasing activity. In the case of the full length (44-amino acid) polypepitide, the leucine analog has full biological activity in the free acid form, unlike the natural growth releasing factor which requires carboxy terminal amidation for full biological activity.

Polypeptides having growth hormone releasing activity

Novel growth hormone releasing factor analogs in which glycine at position 15 is replaced by appropriately selected amino acids demonstrate enhanced potency for the release of growth hormone and the analogs can be administered to a subject having a deficiency of growth hormone.

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

Phosphonoacetic acid derivatives of purine and pyrimidine nucleosides are novel antiviral and/or antineoplastic agents.

Growing community of inventors

Sparta, NJ, United States of America

Edgar P Heimer