PMID- 32628833 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1526-4602 (Electronic) IS - 1525-7797 (Linking) VI - 21 IP - 8 DP - 2020 Aug 10 TI - Monodisperse and Polydisperse PEGylation of Peptides and Proteins: A Comparative Study. PG - 3134-3139 LID - 10.1021/acs.biomac.0c00517 [doi] AB - Although PEGylation is widely used in biomedicine with great success, it suffers from many drawbacks, such as polydispersity, nonbiodegradability, and loss of precursor potency. Recently, the search for polyethylene glycol (PEG) substitutes has attracted considerable attention. Some of the substitutes partially address the drawbacks of PEGs, but sacrifice the "stealth" effect of PEGs and bring in new issues. Herein, we developed monodisperse oligoethylene glycol (M-OEG) polyamides over 5000 Da as biodegradable and monodisperse PEGylation (M-PEGylation) agents, which provided M-PEGylated peptides and proteins with high monodispersity and a biodegradable PEG moiety. Compared to regular PEGylated proteins with a complex "stealth" cloud of PEG, the hydrogen bond interactions between the M-OEG polyamides and proteins provided the M-PEGylated protein with a biodegradable "stealth" cloak. The monodisperse and biodegradable M-PEGylation strategy as well as the peculiar protein-M-OEG polyamide interactions may shed light on many long-lasting issues during the development of PEGylated biologic drugs, such as monodispersity, biodegradability, and tunable conformation. FAU - Wang, Jie AU - Wang J AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. FAU - Deng, Tao AU - Deng T AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. FAU - Liu, Yuntai AU - Liu Y AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. FAU - Chen, Kexin AU - Chen K AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. FAU - Yang, Zhigang AU - Yang Z AUID- ORCID: 0000-0002-4857-4850 AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. FAU - Jiang, Zhong-Xing AU - Jiang ZX AUID- ORCID: 0000-0003-2601-4366 AD - Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200720 PL - United States TA - Biomacromolecules JT - Biomacromolecules JID - 100892849 RN - 0 (Peptides) RN - 0 (Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - *Peptides MH - Polyethylene Glycols MH - *Proteins EDAT- 2020/07/07 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/07/07 06:00 PHST- 2020/07/07 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/07/07 06:00 [entrez] AID - 10.1021/acs.biomac.0c00517 [doi] PST - ppublish SO - Biomacromolecules. 2020 Aug 10;21(8):3134-3139. doi: 10.1021/acs.biomac.0c00517. Epub 2020 Jul 20.