Highly efficient biocatalytic cascade for the diversity-oriented synthesis of complex blood group Sd(a) antigens
GREEN CHEMISTRY
Authors: Zhong, Kan; Ye, Jinfeng; Zhu, Xinhao; Cao, Hongzhi; Liu, Chang-Cheng
Abstract
Sd(a) antigens are a family of widely distributed histo-blood group antigens sharing the Sia alpha 2,3(GalNAc beta 1,4)Gal trisaccharide determinant. Despite their significant biological importance, the synthesis of these complex carbohydrate antigens is challenging. Herein, we report a highly efficient and green synthesis of diverse Sd(a) antigens with different underlying structures and sialic acid forms utilizing 6 multienzyme cascade reaction systems. The multienzyme cascade approach combines sugar nucleotide donor generation enzymes and glycosyltransferases, providing an efficient and convenient approach for the rapid assembly of complex glycans from simple monosaccharide building blocks.
Quantitative proteomics of Naja annulifera (sub-Saharan snouted cobra) venom and neutralization activities of two antivenoms in Africa
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Authors: Tan, Kae Yi; Wong, Kin Ying; Tan, Nget Hong; Tan, Choo Hock
Abstract
Envenomation by Naja annulifera (snouted cobra), a non-spitting African cobra, can result in local tissue damage and fatal paralysis but a species-specific antivenom treatment is currently lacking. In this study, we investigated the quantitative proteome of N. annulifera venom, incorporating HPLC and LC-MS/MSto elucidate the venom toxicity. The immunoreactivities and in vivo neutralization activities of two hetero-specific antivenom products (Premium Serums Pan Africa polyvalent antivenom, PANAF and VINS African polyvalent antivenom, VAPAV) against the venom were subsequently examined. N. annulifera venom comprises 10 toxin families, with three-finger toxin (3FTx) being the most abundantly expressed (similar to 78%). Within 3FTx, cytotoxin is the most dominant form and made up three-quarter of the venom bulk (similar to 74%), whereas alpha-neurotoxins constitute <4% of the total venom proteins. Phospholipase A(2) was undetected in the venom proteome, consistent with the unusual absence of PLA(2) from the venoms of cobras in the Uraeus subgenus. In ELISA, PANAF and VAPAV showed comparable immunoreactivity toward the protein antigens of N. annulifera venom. These antivenoms, despite being raised against hetero-specific venoms, were capable of cross-neutralizing the lethal effect of N. annulifera venom in mice, with PANAF being marginally more potent. (c) 2020 Published by Elsevier B.V.