NMR studies on turn mimetic analogs derived from melanocyte-stimulating hormones.
Oligomers with alpha-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a CDCl3 solution. In order to design an alpha-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on alpha-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-d6 contain a stable 7-membered-ring structure that is similar to a gamma-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.
Cho
Min-Kyu
MK
Department of Biochemistry and Protein Network Research Center, College of Science, Yonsei University, Seoul 120-749, Korea. wlee@spin.yonsei.ac.kr
Kim
Sung-Soo
SS
Lee
Myung-Ryul
MR
Shin
Joon
J
Lee
Jiyong
J
Lim
Sung-Kil
SK
Baik
Ja-Hyun
JH
Yoon
Chang-Ju
CJ
Shin
Injae
I
Lee
Weontae
W
D006860:Hydrogen Bonding; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry*; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
D009074:Melanocyte-Stimulating Hormones