An examination of the steric effects of 5-tert-butylproline on the conformation of polyproline and the cooperative nature of type II to type I helical interconversion
✍ Scribed by Eric Beausoleil; William D. Lubell
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2000
- Tongue
- English
- Weight
- 114 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
The influence of steric effects on the helical geometry and the interconversion of type II to type I polyproline in water was examined by the synthesis and analysis of proline dimers and hexamers containing up to three (2S,5R)-5-tert-butylproline residues. In the dimers, the bulky 5-tert-butyl substituent was found to exert a significant influence on the local prolyl amide geometry such that the predominant trans-isomer in N-(acetyl)prolyl-prolinamide (1) was converted to 63% cis isomer in N-(acetyl)prolyl-5-tert-butylprolinamide (2) as measured by 1 H-nmr spectroscopy. Similarly, the presence of a 5-tert-butyl group on the C-terminal residue in the polyproline hexamer Ac-Pro 5 -t-BuPro-NH 2 (4) produced a local 5-tert-butylprolyl amide population containing 61% cis isomer in water. In spite of the presence of a local prolyl cis amide geometry, the downstream prolyl amides in 4 remained in the trans isomer as determined by NOESY spectroscopy. Conformational analysis by 13 C-nmr and CD spectroscopy indicated that Ac-Pro 6 -NH 2 (3) adopted the all-trans amide polyproline type II helix in water. As the amount of 5-tert-butylproline increased from one to three residues in hexamers 4-6, a gradual destabilization of the polyproline type II helical geometry was observed by CD spectroscopy in water; however, no spectrum was obtained, indicative of a complete conversion to a polyproline type I helix. The implications of these results are discussed with respect to the previously proposed theoretical mechanisms for the helical interconversion of polyproline, which has been suggested to occur by either a cooperative C-to N-terminal isomerization of the prolyl amide bonds or via a conformational intermediate composed of dispersed sequences of prolyl amide cis and trans isomers.