Optimal N-caps for N-terminal helical templates: effects of changes in H-bonding efficiency and charge.
A family of efficient helix-initiating N-terminal caps X-Hel is introduced that expand the scope and versatility of the previously reported reporting conformational template Ac-Hel, (Kemp, D. S.; Allen, T. J.; Oslick, S. J. Am. Chem. Soc. 1995, 117, 6641-6657) and a working principle for predicting cap performance is described, based on structurally specific intramolecular hydrogen bond formation. Replacement of the N-acetyl by urethane, urea, or sulfonamide generated less efficient polypeptide helix inducers. The N-formyl cap is found to be equivalent to the N-acetyl and may provide more convenient quantitative helix reporting properties. Anionic N-caps derived from the series X = (-)O(2)C-(CH(2))(n)-CO, 0 < or = n < or = 3, are superior to N-acetyl, as are N-acylglycyl and N-acyl-beta-aspartyl. The latter pair of caps permit introduction of the X-Hel functionality within a polypeptide chain, allowing control of helicity of a peptide sub-sequence. Applications of these capping functions are discussed. This work has been focused primarily on immediate practical goals directed toward enhancing the maximum helicity of isolated short to medium-sized peptides in aqueous solution, but its developing concepts and working hypotheses are likely to significantly enhance our understanding at a chemical level of the protein folding problem.
Maison
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Department of Chemistry, Room 18-582, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Arce
E
E
Renold
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P
Kennedy
R J
RJ
Kemp
D S
DS
D000577:Amides / Q000737:chemistry; D002942:Circular Dichroism; D004151:Dipeptides / Q000737:chemistry; D006860:Hydrogen Bonding; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013698:Templates, Genetic
D000577:Amides; D004151:Dipeptides; D010455:Peptides