H-VAL-MET-OH

Rats and chicks obtain little or no bioefficacy from the D-isomers of lysine, threonine, arginine, histidine and cystine. D-isomers of the branched-chain amino acids, i.e., leucine, isoleucine and valine (LEU, ILE, VAL) are utilized relatively well by chicks but poorly by rats. D-tryptophan is utilized efficiently by rats and pigs, but inefficiently by chicks, poults, mice and humans. The D-forms of phenylalanine (PHE), tyrosine and methionine (MET) are utilized well by both rats and chicks. Keto and hydroxy analogs of LEU, ILE, VAL, PHE and MET are utilized by both rats and chicks. The L-isomer of the alpha-hydroxy analogs of ILE and PHE has bioactivity while the D-isomer has no bioactivity. D-OH-LEU and D-OH-VAL have bioactivity, but they are less efficacious than their corresponding L-OH analogs. D-OH-MET is a more efficient precursor of L-MET than is L-OH-MET. In general, alpha-keto analogs of LEU, ILE, VAL, PHE and MET are utilized no more efficiently than the active isomeric form of the alpha-OH analogs of these amino acids. The alpha-OH and alpha-keto analogs of ILE are utilized relatively efficiently when used to replace only a portion of L-ILE in a purified amino acid diet for either rats or chicks; utilization of L-ILE analogs is poor, however, when all of the dietary L-ILE is replaced by analog material. In addition to MET and cyst(e)ine, many other dietary sulfur compounds must be considered when dealing with sulfur amino acid bioactivity. Glutathione, taurine, N-acetyl-MET, lanthionine and inorganic sulfate all have sulfur amino acid bioactivity under certain circumstances. Likewise, both oral and endogenous carnosine have histidine bioactivity, and purines, pyrimidines and urea have dispensable amino acid biosynthetic activity.

The title compound, C(56)H(83)N(9)O(9)S·3CH(3)OH, is a methanol tris-olvate of the cyclo-linopeptide cyclo(Met(1)-Leu(2)-Ile(3)-Pro(4)-Pro(5)-Phe(6)-Phe(7)-Val(8)-Ile(9)) (henceforth referred to as CLP-B), which was isolated from flaxseed oil. All the amino acid residues are in an l-configuration based on the CORN rule. The cyclic nona-peptide exhibits eight trans peptide bonds and one cis peptide bond observed between the two proline residues. The conformation is stabilized by an α-turn and two consecutive β-turns each containing a N-H⋯O hydrogen bond between the carbonyl group O atom of the first residue and the amide group H atom of the fourth (α-turn) or the third residue (β-turns), repectively. In the crystal, the components of the structure are linked by N-H⋯O and O-H⋯O hydrogen bonds into chains parallel to the a axis.

Reproducible preparations are given for salts of the following L-amino acid derivatives: Bpoc-Ala-OH, Bpoc-Arg(Mtr)-OH, Bpoc-Asn-OH, Bpoc-Asp(OtBu)-OH, Bpoc-Cys(Acm)-OH, Bpoc-Cys(S-tBu)-OH, Bpoc-Gln-OH, Bpoc-Glu(OtBu)-OH, Bpoc-Gly-OH, Bpoc-Ile-OH, Bpoc-Leu-OH, N-alpha-Bpoc-Lys(epsilon-Boc)-OH, Bpoc-Met-OH, Bpoc-Phe-OH, Bpoc-Pro-OH, Bpoc-Ser(OtBu)-OH, Bpoc-Thr(OtBu)-OH, Bpoc-Tyr-OH, Bpoc-Val-OH. A study of the deblocking of N-alpha-Bpoc peptides in dichloromethane containing 0.5% trifluoroacetic acid revealed that a rapid equilbrium is established between the first-formed monomeric alkene 2-p-biphenylylpropene and the hindered dimer 2,4-bis(p-biphenylyl)-4-methyl-1-pentene. Thioethers were found to be inefficient carbocation scavengers for the deblocking reaction. The most efficient scavengers were found to be thiophenol and benzyl mercaptan, and the following approximate reactivity order was established: benzyl mercaptan approximately thiophenol greater than indole much greater than 1,3-dimethoxybenzene approximately resorcinol greater than 1,3,5-trimethoxybenzene approximately dimethyl sulfide approximately thioanisole.