title: Low molecular weight protamine (LMWP): a nontoxic protamine substitute and an effective cell-penetrating peptide.
abstract: Low molecular weight protamine (LMWP) is a peptide fragment produced in our laboratory from enzymatic digestion of native protamine. More than 30 papers studying the properties and applications of LMWP have been published by our group in various journals since its initial discovery in 1999. Results have shown that LMWP could completely neutralize the anticoagulant functions of both heparin and low molecular weight heparin (LMWH), with reduced antigenicity and cross-reactivity toward the mice-derived anti-protamine antibodies. Aside from its potential as a heparin/LMWH antagonist, LMWP also shows the ability to retard insulin adsorption by the formation of an insoluble complex, making it a less toxic long-lasting insulin product than the conventional neutral protamine Hagedorn (NPH) insulin for diabetic control. Importantly, LMWP (Sequence: VSRRRRRRGGRRRR), with 10 arginine residues in its structure, could function as a cell-penetrating peptide (CPP), also termed protein transduction domain (PTD), to achieve effective intracellular protein or gene delivery in clinical practice. In this paper, we present a thorough review of our work related to LMWP, with the aim of providing readers an insight into its potential to be a clinical protamine substitute as well as a non-toxic cell penetrating peptide applicable to achieve intracellular protein and gene delivery.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300072, PR China; State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
authors.forename: Huining
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
authors.forename: Junxiao
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
authors.forename: Ergang
authors.initials: E
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300072, PR China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Liang
authors.affiliation: State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300072, PR China; State Key Laboratory for Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA; Department of Molecular Medicine and Biopharmaceutical Sciences, College of Medicine & College of Pharmacy, Seoul National University, Seoul, South Korea. Electronic address: vcyang@med.umich.edu.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D003429:Cross Reactions / Q000187:drug effects / Q000276:immunology; D004339:Drug Compounding; D006494:Heparin Antagonists / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D011479:Protamines / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D011487:Protein Conformation
chemical_list: D000906:Antibodies; D057846:Cell-Penetrating Peptides; D006494:Heparin Antagonists; D010446:Peptide Fragments; D011479:Protamines
keywords: Cell-penetrating peptide (CPP); Heparin antagonist; Low molecular weight protamine; Protamine; Protein transduction domain (PTD)