報告題目⚾️：Introducing Lasso Peptides as Molecular Scaffold for Drug Design

報告人👵🏿：Mohamed A. Marahiel

報告時間：2012年5月8日（10:00）

報告地點：徐匯校區哲生館1樓會議室

摘要🚵🏿‍♀️：A widespread class of therapeutically important natural products are of peptide origin. They are either assembled on the ribosome (such as lasso Peptides) followed by an extensive post-translational modification or are produced independent of the ribosome (nonribosomally) using large multi-modular-enzymes, the so called nonribosomal peptide synthetases (NRPS).
One class of macrocyclic peptides we studying are of ribosomal origin. These bioactive natural products synthesized by bacteria are composed of 16-21 canonical amino acids and show unusual and complex lasso-structures. They share an N-terminal 8/9-residue macrolactam ring, generated upon a condensation reaction between the -NH2 group of Gly1/Cys1 and the carboxyl side chain of Asp/Glu at position 8 or 9. The tail (8 - 13 residues) threads through the macrocycle and is trapped by steric hindrance of bulky side chains within the ring, generating a common lariat-protoknot structure of unmatched high stability 1,2,3. Their biological activities range from inhibition of HIV replication to blockage of the bacterial RNA polymerase. In this superfamily of lasso-structure peptides, we are interested in studying their NMR-structures and enzymatic biosynthesis as well as in developing methods for their reengineering as a molecular scaffold for drug design.

聯系人:林雙君