Type 1A Mutants Research - from Japan

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Abstract from J Pept Res. 2003 Aug;62(2):78-87.

Conformation of the transmembrane domains in peripheral myelin protein

22. Part 1. Solution-phase synthesis and circular dichroism study of

protected 17-residue partial peptides in the first putative

transmembrane domain.

Yamada K, Sato J, Oku H, Katakai R.

Department of Chemistry, Gunma University, Gunma 376-8515, Japan.

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited

peripheral neuropathy. DNA duplication and point mutation of the gene

encoding peripheral myelin protein 22 (PMP22) have been found in CMT

type 1A dominants. To investigate the influence of the point mutation of

PMP22 on the secondary structure, protected partial peptides in the

putative first transmembrane domain, wild type

Boc-IVLH(Bom)VAVLVLLFVSTIV-OMe (1) and its Pro16 mutant

Boc-IVLH(Bom)VAVPVLLFVSTIV-OMe (2) were synthesized. Circular dichorism

(CD)-spectral analysis suggested that peptide 1 adopts a stable

alpha-helical conformation in membrane-mimetic

solvent,1-BuOH/1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) system.

On the contrary, the mutant 2 favors beta-sheet conformation in the same

solvent system. Interestingly, alpha-helix to beta-sheet transition of 2

was observed at higher contents of 1-BuOH than 70%.