Journal
JOURNAL OF CONTROLLED RELEASE
Volume 193, Issue -, Pages 63-73Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.05.056
Keywords
Low molecular weight protamine; Protein transduction domain (PTD); Cell-penetrating peptide (CPP); Heparin antagonist; Protamine
Funding
- National Natural Science Foundation of China (NSFC) [81361140344]
- Tianjin Municipal Science and Technology Commission [12JCZDJC34000]
- School of Pharmacy
- Fudan University & the Open Project Program of Key Lab of Smart Drug Delivery (Fudan University)
- Ministry of Education, China [SDD2013-04]
- National Key Basic Research Program of China [2013CB932502]
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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. (C) 2014 Elsevier B.V. All rights reserved.
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