Synthesis of decapeptide of L-aspartic acid and benzyl-L-aspartic acid by solid phase peptide synthesis.
Polyene macrolide amphotericin B (AmB) is the drug of choice for the treatment of disseminated fungal infections. However, because of its pronounced side effects, the drug has limited applicability. There are few interesting reports, which state that co-administration of the drug with homo-peptide of polyaspartic acid reduces the side effects of the drug. In our present study, an approach has been made to systematically synthesize low molecular weight heteropeptides consisting of L-aspartic acid and its derivative. It was hypothesized that such heteropeptides will reduce the toxic side effects of the drug by facile hydrophobic binding between the polymer and the drug. We have employed the strategy of solid phase peptide synthesis (SPPS) to synthesize low molecular weight hetero-peptides by using L-aspartic acid and benzyl-L-aspartic acid to induce the hydrophobic binding between the peptide and the drug. In future, the proposed methodology can be employed to tailor other polypeptides substituted with benzyl groups to reduce the nephrotoxicity of AmB.
Yoo
Bong K
BK
College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, 712-749, Korea.
Miah
M A Jalil
MA
Lee
Eung-Seok
ES
Han
Kun
K
D001224:Aspartic Acid / Q000031:analogs & derivatives*; D001593:Benzyl Compounds; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis*
D001593:Benzyl Compounds; D010455:Peptides; D001224:Aspartic Acid