Creatinine, lactam and cyclic peptide formation by the action of C2N2 on creatine, omega-amino acids and peptides.
Cyanogen, C2N2, affords a means to drive intramolecular conversion of ammonium salts to amides. Unlike other carboxyl activating agents, such as carbodiimides, used in peptide syntheses expressly to drive intermolecular condensations to form amide (peptide) bonds, C2N2 appears restricted to driving only intramolecular condensations. Rates decreased as a function of solvent composition as follows: organic much greater than 70%-80% aqueous organic much greater than 50% aqueous organic greater than H2O. Temperature dependence was also a function of solvent composition. Rates did not strongly reflect steric constraints with beta-lactams and epsilon-lactams forming at comparable rates to rates for gamma- and delta-lactam formation; likewise L-Leu-L-Leu cyclized at about the same rate as L-Leu-D-Leu. Pro-Pro is well documented as having a salt-bridged structure in a variety of solvents where it cyclized extremely rapidly. The reaction is proposed to be dependent on reaction of C2N2 with salt-bridges on the basis of 1) its preponderant if not exclusively intramolecular nature, 2) its solvent dependence, 3) its temperature dependence and 4) the conversion of known salt-bridged structures to amides. This reaction is a model for the observed rapid reaction of salt bridges in proteins.
Day
R A
RA
Department of Chemistry, University of Cincinnati, OH 45221-0172.
Tharp
R L
RL
Madis
M E
ME
Wallace
J A
JA
Silanee
A
A
Hurt
P
P
Mastruserio
N
N
D000596:Amino Acids / Q000737:chemistry*; D003404:Creatinine / Q000138:chemical synthesis*; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis*; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*
D000596:Amino Acids; D007769:Lactams; D009570:Nitriles; D010456:Peptides, Cyclic; C011206:cyanogen; D003404:Creatinine