biostudies-literatureUnknown10(45)Dhurjad PConformational diversity in conopeptides, Be828 and Li833, for which sequences are identified from Conus betulinus and Conus lividus has been explored in the present study. Be828 and Li833 have 23-membered rings with two consecutive prolines at positions 2/3 and 4/5, respectively, an unusual phenomenon observed in contryphans. These peptides provided an excellent scope to probe distinct conformational states, i.e., cis-trans isomerization around Xaa-Pro and Pro-Pro bonds. NMR analysis revealed that Be828 exists as a single trans (C1-P2)/trans (P2-P3) conformation, whereas Li833 exists in four distinct conformers across the consecutive proline bonds. Studies on synthetic analogues disclosed that the conformational heterogeneity in Li833 is influenced by the constACS omega54030-54038https://www.ebi.ac.uk/biostudies/studies/S-EPMC12631695biostudies-literatureConformational Heterogeneity of Pro-Pro Containing 23-Membered Ring Conopeptides by NMR.PMC12631695Dhurjad PSonti RShaik KDannarm SRWanjari PfalseConformational Heterogeneity of Pro-Pro Containing 23-Membered Ring Conopeptides by NMR.Conformational diversity in conopeptides, Be828 and Li833, for which sequences are identified from Conus betulinus and Conus lividus has been explored in the present study. Be828 and Li833 have 23-membered rings with two consecutive prolines at positions 2/3 and 4/5, respectively, an unusual phenomenon observed in contryphans. These peptides provided an excellent scope to probe distinct conformational states, i.e., cis-trans isomerization around Xaa-Pro and Pro-Pro bonds. NMR analysis revealed that Be828 exists as a single trans (C1-P2)/trans (P2-P3) conformation, whereas Li833 exists in four distinct conformers across the consecutive proline bonds. Studies on synthetic analogues disclosed that the conformational heterogeneity in Li833 is influenced by the const2025-01-01T00:00:00Z2025 Nov2026-06-05T18:43:10.935Z2026-05-20T03:13:53.595ZS-EPMC126316954128080110.1021/acsomega.5c05404