Switching of turn conformation in an aspartate anion peptide fragment by NH · · · O− hydrogen bonds

• Published in: Biopolymers Vol. 80; no. 2-3; pp. 233 - 248
• Main Authors: Onoda, Akira, Yamamoto, Hitoshi, Yamada, Yusuke, Lee, Keonil, Adachi, Seiji, Okamura, Taka-aki, Yoshizawa-Kumagaye, Kumiko, Nakajima, Kiichiro, Kawakami, Toru, Aimoto, Saburo, Ueyama, Norikazu
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2005
• Subjects: Amino Acid Sequence; Anions - chemistry; aspartate anion; Aspartic Acid - chemistry; aspartic acid protease model peptides; Circular Dichroism; conserved amino acid fragments; deprotonation; hairpin turn; Hydrogen Bonding; hydrogen bonds; Hydrogen-Ion Concentration; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; Peptide Fragments - chemistry; Protein Conformation; protonation; turn conformation
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.20187

Aspartic acid protease model peptides Z–Phe–Asp(COOH)–Thr–Gly–Ser–Ala–NHCy (1) and AdCO–Asp(COOH)–Val–Gly–NHBzl (3), and their aspartate anions (NEt4)[Z–Phe–Asp(COO−)–Thr–Gly–Ser–Ala–NHCy] (2) and (NEt4)[AdCO–Asp(COO−)–Val–Gly–NHBzl] (4), having an invariant primary sequence of the Asp–X(Thr,Ser)—Gly fragment, were synthesized and characterized by 1H‐NMR, CD, and infrared (IR) spectroscopies. NMR structure analyses indicate that the Asp Oδ atoms of the aspartate peptide 2 are intramolecularly hydrogen‐bonded with Gly, Ser, Ala NH, and Ser OH, supporting the rigid β‐turn‐like conformation in acetonitrile solution. The tripeptide in the aspartic acid 3 forms an inverse γ‐turn structure, which is converted to a β‐turn‐like conformation because of the formation of the intramolecular NH · · · O− hydrogen bonds with the Asp Oδ in 4. Such a conformational change is not detected between dipeptides AdCO–Asp(COOH)–Va–NHAd (5) and (NEt4)[AdCO–Asp(COO−)–Val–NHAd] (6). The pKa value of side‐chain carboxylic acid (5.0) for 3 exhibits a lower shift (0.3 unit) from that of 5 in aqueous polyethyleneglycol lauryl ether micellar solution. NMR structure analyses for 3 in an aqueous micellar solution indicate that the preorganized turn structure, which readily forms the NH · · · O− hydrogen bonds, lowers the pKa value and that resulting hydrogen bonds stabilize the rigid conformation in the aspartate anion state. We found that the formation of the NH · · · O− hydrogen bonds involved in the hairpin turn is correlated with the protonation and deprotonation state of the Asp side chain in the conserved amino acid fragments. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005