56612-01-2Relevant academic research and scientific papers
Creatinyl amino acids-new hybrid compounds with neuroprotective activity
Burov, Sergey,Leko, Maria,Dorosh, Marina,Dobrodumov, Anatoliy,Veselkina, Olga
experimental part, p. 620 - 626 (2012/04/04)
Prolonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood-brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alternative pathway is of great importance for the treatment of acute and chronic neurological diseases including stroke, traumatic brain injury and hereditary CRT deficiency. Here we describe synthesis of new hybrid compounds-creatinyl amino acids, their neuroprotective activity in vivo and stability to degradation in different media. The title compounds were synthesized by guanidinylation of corresponding sarcosyl peptides or direct creatine attachment using isobutyl chloroformate method. Addition of lipophilic counterion (p-toluenesulfonate) ensures efficient creatine dissolution in DMF with simultaneous protection of guanidino group towards intramolecular cyclization. It excludes the application of expensive guanidinylating reagents, permits to simplify synthetic procedure and adapt it to large-scale production. The biological activity of creatinyl amino acids was tested in vivo on ischemic stroke and NaNO2-induced hypoxia models. One of the most effective compounds-creatinyl-glycine ethyl ester increases life span of experimental animals more than two times in hypoxia model and has neuroprotective action in brain stroke model when applied both before and after ischemia. These data evidenced that creatinyl amino acids can represent promising candidates for the development of new drugs useful in stroke treatment. Copyright
The L-Proline Residue as a 'Break-point' in Metal - Peptide Systems
Pettit, Leslie D.,Steel, Ian,Formicka-Kozlowska, Grazyna,Tatarowski, Tomasz,Bataille, Michael
, p. 535 - 540 (2007/10/02)
Results are reported of a potentiometric and spectrophotometric study of the H+ and Cu2+ complexes of the tetrapeptides X-Gly-Gly-Gly, Gly-X-Gly-Gly, Gly-Gly-X-Gly, and Gly-Gly-Gly-X where X is the proline (Pro) and sarcosine (Sar) residue (Gly=glycine).All the tetrapeptides (HL) form the series of complexes , -1L>, -2L>, and -3L> (charges omitted).The ligands Gly-X-Gly-Gly also form the bis-complex, .When inserted in a peptide chain the Pro and Sar residues cannot co-ordinate to Cu2+ through their peptide nitrogens since they do not possess ionizable protons.In addition the Pro residue tends to force the peptide chain to form a 'β-turn' and so adopt a 'bent' conformation.These studies demonstrate the formation of a large chelate ring when tetrapeptides containing Pro (and , to a smaller extent, Sar) in the second or third positions co-ordinate to Cu2+.This ring spans the terminal residues of the peptide chain and locks the peptide into a 'bent' or 'horse-shoe' shaped conformation.Cu2+ could therefore play an important role in activating oligopeptides (e.g. neuropeptides) containing proline.
