Document Detail


Azido gauche effect on the backbone conformation of β-azidoalanine peptides.
MedLine Citation:
PMID:  20849143     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To study the azido gauche effect on the backbone conformation of β-azidoalanine (Aza) dipeptide (AAD, Ac-Aza-NHMe) and tripeptide (AAT, Ac-Aza-Aza-NH(2)), we used spectroscopic methods in combination with quantum chemistry calculations and molecular dynamics (MD) simulations. From the (1)H NMR coupling constants and (1)H,(1)H NOESY experimental data, we found that AAD in water mainly adopts a seven-membered cyclic (C(7)) rather than polyproline II (P(II)) backbone conformation and prefers the gauche- (g(-)) side-chain conformer. From the amide I IR absorption and circular dichroism (CD) spectra, the backbone conformation of AAD in water is found to deviate from P(II) but is rather close to C(7). Thus, the backbone conformation of AAD differs from that of alanine dipeptide (AD, Ac-Ala-NHMe), which is mainly P(II) in water. The underlying origin of the backbone conformational difference between AAD and AD in water was elucidated by quantum chemistry calculations with density functional theory (DFT). It was found that the C(7)/g(-) conformer is the lowest energy structure of an isolated AAD. Here, the β-azido group forms intramolecular electrostatic interactions with two neighboring peptide bonds, which are facilitated by the azido gauche effect. Thus, the β-azido group appears to be responsible for directing the peptide backbone conformation toward the C(7) structure. The quantum mechanical/molecular mechanical (QM/MM) MD simulations show that AAD in water adopts neither P(II) nor right-handed α-helix (α(R)) and prefers the g(-) conformer. Thus, the intramolecular electrostatic interactions between the β-azido group and two nearby peptide bonds are also found even in the aqueous solution structure of AAD. Consequently, the β-azido group appears to be an effective C(7)-conformation-directing element, which may also be useful for tuning the structures of other amino acids and polypeptides.
Authors:
Kwang-Im Oh; Woosung Kim; Cheonik Joo; Dong-Geun Yoo; Hogyu Han; Geum-Sook Hwang; Minhaeng Cho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  114     ISSN:  1520-5207     ISO Abbreviation:  J Phys Chem B     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-07     Completed Date:  2011-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13021-9     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Korea University, Seoul 136-701, Korea.
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MeSH Terms
Descriptor/Qualifier:
Alanine / analogs & derivatives*,  chemistry
Azides / chemistry*
Circular Dichroism
Molecular Dynamics Simulation
Peptides / chemistry*
Protein Structure, Secondary
Quantum Theory
Spectrophotometry, Infrared
Static Electricity
Chemical
Reg. No./Substance:
0/Azides; 0/Peptides; 56-41-7/Alanine; 88192-18-1/azidoalanine

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