High impact information on Cyclohexylalanine

• Para-aminophenylalanine 10 and O-ethyltyrosine 10 substitutions yielded antagonists potent in vitro, but His(10), 3,3'-diphenylalanine 10, 2-naphthylalanine 10, and cyclohexylalanine 10 modifications were detrimental [1].
• A series of replacements for the C-terminal Leu established that residues containing a lipophilic side chain were most effective, with cyclohexylalanine having the greatest potency (3g, IC50 = 0.36 +/- 0.06 microM) [2].
• These inhibitors, which are of the hydroxyethylene and statine types, respectively, possess a cyclohexylalanine side chain at P1 and have interesting functionalities at the P3 position which, until now, have not been subjected to crystallographic analysis [3].
• Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine [4].
• Furthermore, a shortening of the C-terminal part of our peptide analogues and the replacement of the leucine residue in P1 by a cyclohexylalanine leads to the tripeptide analogue 12 a potent renin inhibitor (IC50 = 3.5 x 10(-9) M) [5].

Associations of Cyclohexylalanine with other chemical compounds

• We have selected three hydrophilic and charged residues--glutamic acid, histidine, and lysine--as well as three hydrophobic residues--cycloleucine, cyclohexylalanine, and naphthyl-(1)-alanine--to replace the A14 Tyr [6].

References