Synthesis and evaluation of constrained peptide analogues related to the N-terminal region of human growth hormone.
The synthesis and incorporation of two different isomeric gamma-lactam structures into peptide analogues related to hGH [6-13] are described. These peptide analogues and the corresponding aspartimide analogue have been tested for hypoglycemic activity with the intravenous insulin tolerance test. One lactam structure is of the type developed by Freidinger and co-workers, while the isomeric gamma-lactam structure represents a new constrained synthon for use in peptide synthesis. We have found that the hGH [6-13] peptide analogue incorporating the Freidinger lactam was more potent and longer lasting than the aspartimide peptide analogue. The hGH [6-13] peptide analogue incorporating the new gamma-lactam has diminished hypoglycemic activity. The relative biological activities of the three peptide analogues and the possible conformational implications at the physiological site of action are discussed.
Ede
N J
NJ
Dept. of Biochemistry, Monash University, Clayton, Victoria, Australia.
Lim
N
N
Rae
I D
ID
Ng
F M
FM
Hearn
M T
MT
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C037849:somatotropin (6-13); D013006:Growth Hormone