Cis-trans isomerization of amide bonds plays critical roles in protein molecular recognition, protein folding, protein misfolding, and disease. Aromatic-proline sequences are particularly prone to exhibit cis amide bonds. The roles of residues adjacent to a tyrosine-proline residue pair on cis-trans isomerism were examined. A short series of peptides XYPZ was synthesized and cis-trans isomerism was analyzed. Based on these initial studies, a series of peptides XYPN, X = all 20 canonical amino acids, was synthesized and analyzed by NMR for i residue effects on cis-trans isomerization. The following effects were observed: (a) aromatic residues immediately preceding Tyr-Pro disfavor cis amide bonds, with K(trans/cis)= 5.7-8.0, W > Y > F; (b) proline residues preceding Tyr-Pro lead to multiple species, exhibiting cis-trans isomerization of either or both X-Pro amide bonds; and (c) other residues exhibit similar values of K(trans/cis) (= 2.9-4.2), with Thr and protonated His exhibiting the highest fraction cis. beta-Branched and short polar residues were somewhat more favorable in stabilizing the cis conformation. Phosphorylation of serine at the i position modestly increases the stability of the cis conformer. In addition, the effect of the i+3 residue was examined in a limited series of peptides TYPZ. NMR data indicated that aromatic residues, Pro, Asn, Ala, and Val at the i+3 residue all favor cis amide bonds, with aromatic residues and Asn favoring more compact phi at Tyr(cis) and Ala and Pro favoring more extended phi at Tyr(cis). D-Alanine at the i+3 position particularly disfavors cis amide bonds.

Type-2 diabetes is a leading cause of death and disability. Emerging evidence suggests that ultraviolet radiation or sun exposure may limit its development. We used freely available online datasets to evaluate the associations between solar radiation and type-2 diabetes prevalence across Australia. We extracted prevalence data for 1822 postcodes from the Australian Diabetes Map on 25 January 2020. Daily solar radiation data averaged over 30-years (1990–2019) were collated from online databases (Australian Bureau of Meteorology). Population-weighted linear regression models were adjusted for covariates at the postcode level including socioeconomic status (IRSAD), remoteness, mean age, gender, Aboriginal and Torres Strait Islander status, as well as mean annual ambient temperature (1961–1990) and rainfall (1981–2010). A consistent inverse correlation was observed between type-2 diabetes prevalence and solar radiation, after adjusting for these covariates (ß (coefficient of regression) = −0.045; 95% CI: −0.086, −0.0051; p = 0.027). However, the relative contribution of solar radiation towards type-2 diabetes prevalence was small (2.1%) in this model. Other significant correlations between type-2 diabetes prevalence and covariates included: socioeconomic status (ß = −0.017; 95% CI: −0.017, −0.016; p < 0.001), mean age (ß = 0.041; 95% CI: 0.028, 0.054; p < 0.015), remoteness (ß = −0.05; 95% CI: −0.088, −0.011; p < 0.001) and rainfall (ß = −0.0008; 95% CI: −0.00097, −0.00067; p < 0.001). In conclusion, in Australian postcodes, higher levels of solar radiation and rainfall was associated with reduced type-2 diabetes prevalence. Further studies are needed that consider lifestyle covariates such as physical activity.

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