Analogues of luteinizing hormone-releasing hormone with modification in position 3.

Small peptide inhibitors of smooth muscle myosin light chain kinase

“…Nonetheless we have shown (vide infra) that Ser is not phosphorylated in several of our best inhibitors. Furthermore, substitution of Thr (16) and Cys (17) for Ser in the peptides resulted in inhibitors with equal or better inhibition against the native enzyme. One attractive hypothesis was that the Ser or surrogate was hydrogen bonding to a phosphate anion of the -phosphate of ATP in the active site.…”

“…We have prepared synthetic peptides modeled on the template of 10 in which individual amino acids were specifically replaced (at Ser,(16)(17)(18)(19)(20)(21)(22)(23)(24)at Asn,(25)(26)(27)(28)(29)(30)(31)at Val,(32)(33)(34)(35)(36)at Phe,(37)(38)(39)(40)(41)(42)(43)(44)(45)and at AlaOBzl,(46)(47)(48)(49)(50)(51)(52)(53)(54) with other residues. The importance of individual amino acid contributions to the structure-activity relationship for enzyme inhibition was evaluated with these compounds.…”

“…Natert-Butyloxycarbonyl and FMOC amino acids and benzyl esters were supplied by Bachem, Inc., Sigma Chemical Co., or Chemical Dynamics Corp. [ -32 ] was obtained from ICN, calmodulin was purchased from Boehringer-Mannheim, and all other chemicals were obtained from the Sigma or Aldrich Chemical Co. The nonstandard amino acids, Bpa and Dpa, were prepared according to literature procedures as previously described.16,17 Boc amino acids were prepared as described by Tarbel et al 16 All reactions were carried out under an inert atmosphere. NMR spectra were recorded on Varían XL200, XL300, or XL400 spectrometers.…”

Synthesis of 3‐(3‐pyridyl)‐ and 3‐(3‐benzo[b]thienyl)‐D‐alanine

“…Enzymatic resolutions of DL-3-Pal derivatives have been reported for Na-benzoyl-DL3-Pal with a-chymotrypsin (7), for Naacetyl-DL-3-Pal with porcine kidney acylase (8), and for Na-benzoyl-DL3-Pal methyl ester with subtilisin Carlsberg (9). The (14) and for N-benzyloxycarbonyl-Gly-DL-Bal with carboxypeptidase A (12). The general method we employed consisted of a modified malonic ester synthesis initially developed by Berger et al (1 5 ) and is outlined in Scheme 1, This procedure involved an initial condensation of the sodium salt of diethyl acetamidomalonate with the appropriate halide (0 followed by partial hydrolysis to the mono ester (IZI).…”

Synthesis, Resolution and Charge‐donor Properties of Six Tryptophan Analogues

“…The observation that the LH-RH analogue, having the weak electron donor 3-(2-naphthyl)-L-alanine instead of tryptophan in position 3, has a rather high LH-activity (Prasad et al, 1975;Yabe et al, 1976) may well be an indication that the contribution of the relevant residue to the activity is merely due to lipophilic interaction. The role of essential tryptophan residues in peptide chains can certainly not be attributed to its donor properties alone.…”