Modulation of an N→π* Interaction with α-fluoro Groups

Overview

Journal ARKIVOC

Specialty Chemistry

Date 2011 Jun 7

PMID 21643549

Citations 10

Authors

Amit Choudhary

Charles G Fry

Ronald T Raines

Affiliations

Soon will be listed here.

Abstract

Noncovalent interactions play an essential role in biological and chemical processes. In the main chain of common protein secondary structures, the lone pair (n) of a carbonyl oxygen is delocalized into the antibonding orbital (π*) of the subsequent carbonyl group. Herein, experimental and computational data reveal that this n→π* interaction can be attenuated by the inductive electron withdrawal of one or two α-fluoro groups in the donor. The steric effect of three α-fluoro groups, however, overcomes the inductive withdrawal. These data evoke a means to modulate the n→π* interaction in peptides, proteins, and other systems.

Citing Articles

Electronic and Steric Control of n→π* Interactions: Stabilization of the α-Helix Conformation without a Hydrogen Bond.

Wenzell N, Ganguly H, Pandey A, Bhatt M, Yap G, Zondlo N Chembiochem. 2018; 20(7):963-967.

PMID: 30548564 PMC: 6458595. DOI: 10.1002/cbic.201800785.

The n→π* Interaction.

Newberry R, Raines R Acc Chem Res. 2017; 50(8):1838-1846.

PMID: 28735540 PMC: 5559721. DOI: 10.1021/acs.accounts.7b00121.

Reciprocal carbonyl-carbonyl interactions in small molecules and proteins.

Rahim A, Saha P, Jha K, Sukumar N, Sarma B Nat Commun. 2017; 8(1):78.

PMID: 28724906 PMC: 5517579. DOI: 10.1038/s41467-017-00081-x.

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators.

Syrpas M, Ruysbergh E, Stevens C, De Kimpe N, Mangelinckx S Beilstein J Org Chem. 2014; 10:2539-49.

PMID: 25383125 PMC: 4222389. DOI: 10.3762/bjoc.10.265.

n→π* interactions engender chirality in carbonyl groups.

Choudhary A, Newberry R, Raines R Org Lett. 2014; 16(13):3421-3.

PMID: 24926562 PMC: 4096190. DOI: 10.1021/ol5012967.

References

Shoulders M, Guzei I, Raines R . 4-chloroprolines: synthesis, conformational analysis, and effect on the collagen triple helix. Biopolymers. 2007; 89(5):443-54. PMC: 2802577. DOI: 10.1002/bip.20864. View

Shoulders M, Satyshur K, Forest K, Raines R . Stereoelectronic and steric effects in side chains preorganize a protein main chain. Proc Natl Acad Sci U S A. 2010; 107(2):559-64. PMC: 2818912. DOI: 10.1073/pnas.0909592107. View

Maccallum P, POET R . Coulombic attractions between partially charged main-chain atoms stabilise the right-handed twist found in most beta-strands. J Mol Biol. 1995; 248(2):374-84. DOI: 10.1016/s0022-2836(95)80057-3. View

Fischer F, Wood P, Allen F, Diederich F . Orthogonal dipolar interactions between amide carbonyl groups. Proc Natl Acad Sci U S A. 2008; 105(45):17290-4. PMC: 2582285. DOI: 10.1073/pnas.0806129105. View

Fischer F, Schweizer W, Diederich F . Molecular torsion balances: evidence for favorable orthogonal dipolar interactions between organic fluorine and amide groups. Angew Chem Int Ed Engl. 2007; 46(43):8270-3. DOI: 10.1002/anie.200702497. View

Bretscher L, Jenkins C, Taylor K, DeRider M, Raines R . Conformational stability of collagen relies on a stereoelectronic effect. J Am Chem Soc. 2001; 123(4):777-8. DOI: 10.1021/ja005542v. View

ANFINSEN C . Principles that govern the folding of protein chains. Science. 1973; 181(4096):223-30. DOI: 10.1126/science.181.4096.223. View

Pervushin K, Ono A, Fernandez C, Szyperski T, Kainosho M, Wuthrich K . NMR scalar couplings across Watson-Crick base pair hydrogen bonds in DNA observed by transverse relaxation-optimized spectroscopy. Proc Natl Acad Sci U S A. 1998; 95(24):14147-51. PMC: 24341. DOI: 10.1073/pnas.95.24.14147. View

Hof F, Scofield D, Schweizer W, Diederich F . A weak attractive interaction between organic fluorine and an amide group. Angew Chem Int Ed Engl. 2004; 43(38):5056-9. DOI: 10.1002/anie.200460781. View

10.

Jakobsche C, Choudhary A, Miller S, Raines R . n --> pi* Interaction and n)(pi Pauli repulsion are antagonistic for protein stability. J Am Chem Soc. 2010; 132(19):6651-3. PMC: 2874455. DOI: 10.1021/ja100931y. View

11.

Horng J, Raines R . Stereoelectronic effects on polyproline conformation. Protein Sci. 2005; 15(1):74-83. PMC: 2242370. DOI: 10.1110/ps.051779806. View

12.

Kotch F, Guzei I, Raines R . Stabilization of the collagen triple helix by O-methylation of hydroxyproline residues. J Am Chem Soc. 2008; 130(10):2952-3. PMC: 2802593. DOI: 10.1021/ja800225k. View

13.

Paulini R, Muller K, Diederich F . Orthogonal multipolar interactions in structural chemistry and biology. Angew Chem Int Ed Engl. 2005; 44(12):1788-805. DOI: 10.1002/anie.200462213. View

14.

Gorske B, Bastian B, Geske G, Blackwell H . Local and tunable n-->pi* interactions regulate amide isomerism in the peptoid backbone. J Am Chem Soc. 2007; 129(29):8928-9. DOI: 10.1021/ja071310l. View

15.

Maccallum P, POET R . Coulombic interactions between partially charged main-chain atoms not hydrogen-bonded to each other influence the conformations of alpha-helices and antiparallel beta-sheet. A new method for analysing the forces between hydrogen bonding groups in.... J Mol Biol. 1995; 248(2):361-73. DOI: 10.1016/s0022-2836(95)80056-5. View

16.

DeRider M, Wilkens S, Waddell M, Bretscher L, Weinhold F, Raines R . Collagen stability: insights from NMR spectroscopic and hybrid density functional computational investigations of the effect of electronegative substituents on prolyl ring conformations. J Am Chem Soc. 2002; 124(11):2497-505. DOI: 10.1021/ja0166904. View

17.

Dill K . Dominant forces in protein folding. Biochemistry. 1990; 29(31):7133-55. DOI: 10.1021/bi00483a001. View

18.

Jenkins C, Lin G, Duo J, Rapolu D, Guzei I, Raines R . Substituted 2-azabicyclo[2.1.1]hexanes as constrained proline analogues: implications for collagen stability. J Org Chem. 2004; 69(25):8565-73. DOI: 10.1021/jo049242y. View

19.

Pomerantz W, Hadley E, Fry C, Gellman S . In situ monitoring of backbone thioester exchange by 19F NMR. Chembiochem. 2009; 10(13):2177-81. PMC: 2874940. DOI: 10.1002/cbic.200900380. View

20.

Gorske B, Stringer J, Bastian B, Fowler S, Blackwell H . New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems. J Am Chem Soc. 2009; 131(45):16555-67. PMC: 3175426. DOI: 10.1021/ja907184g. View