Interplay between Cα Methylation and Cα Stereochemistry in the Folding Energetics of a Helix-Rich Miniprotein.

The α-helix is an abundant and functionally important element of protein secondary structure, which has motivated intensive efforts toward chemical strategies to stabilize helical folds. One such method is the incorporation of non-canonical backbone composition through an additional methyl substituent at the Cα atom. Examples of monomers include the achiral 2-aminoisobutyric acid (Aib) with geminal dimethyl substitution and chiral analogues with one methyl and one non-methyl substituent.

Structural and Functional Mimicry of the Antimicrobial Defensin Plectasin by Analogues with Engineered Backbone Composition.

The threat posed by bacteria resistant to common antibiotics creates an urgent need for novel antimicrobials. Non-ribosomal peptide natural products that bind Lipid II, such as vancomycin, represent a promising source for such agents. The fungal defensin plectasin is one of a family of ribosomally produced miniproteins that also exert antimicrobial activity via Lipid II binding.

Application of artificial backbone connectivity in the development of metalloenzyme mimics.

Metal-dependent enzymes are abundant and vital catalytic agents in nature. The functional versatility of metalloenzymes has made them common targets for improvement by protein engineering as well as mimicry by de novo designed sequences. In both strategies, the incorporation of non-canonical cofactors and/or non-canonical side chains has proved a useful tool.

Backbone Modification in a Protein Hydrophobic Core.

Targeted protein backbone modification can recreate tertiary structures reminiscent of folds found in nature on artificial scaffolds with improved biostability. Incorporation of altered monomers in such entities is typically limited to sites distant from the hydrophobic core to avoid potential disruptions to folding. This is limiting, as it is advantageous in some applications to incorporate artificial connectivity at buried sites.

How warm are political interactions? A new measure of affective fractionalization.

Affective polarization measures account for partisans' feelings towards their own party versus its opponent(s), but not for how likely partisans are to encounter co-partisans versus out-partisans. However, the intensity of out-party dislike and the probability with which this comes into play both determine the social impact of cross-party hostility. We develop an affective fractionalization measure that accounts for both factors, and apply it to longitudinal survey data from 20 Western publics.