Synthesis and characterization of arginine-glycine-aspartic peptides conjugated poly(lactic acid-co-L-lysine) diblock copolymer.
A biodegradable Copolymer of poly(lactic acid-co-lysine)(PLA-PLL) was synthesized by a modified method and novel Arginine-Glycine-Aspartic (RGD) peptides were chemical conjugated to the primary epsilon-amine groups of lysine components in four steps: I to prepare the monomer of 3-(Nepsilon-benzoxycarbonyl-L-lysine)-6-L-methyl-2,5-morpholinedione; II to prepare diblock copolymer poly(lactic acid-co-(Z)-L-lysine) (PLA-PLL(Z)) by ring-opening polymerization of monomer and L,L-lactide with stannous octoate as initiator; III to prepare diblock copolymer PLA-PLL by deprotected the copolymer PLA-PLL(Z) in HBr/HoAc solution; IV the reaction between RGD and the primary epsilon-amine groups of the PLA-PLL. The structure of PLA-PLL-RGD and its precursors were conformed by FTIR-Raman and 1H NMR. Low weight average molecular weight (9,200 g/mol) of the PLA-PLL was obtained and its PDI is 1.33 determined by GPC. The PLA-PLL contained 2.1 mol% lysine groups as determined by 1H NMR using the lysine protecting group's phenyl protons. Therefore, the novel RGD-grafted diblock copolymer is expected to find application in drug carriers for tumor therapy or non-viral DNA carriers for gene therapy.
Yu
Hui
H
State Key Lab for Modification of Chemical Fibers & Polymer Materials, College of Materials Science & Engineering, Donghua University, Shanghai 200051, China.
Guo
Xiaojuan
X
Qi
Xueliang
X
Liu
Peifeng
P
Shen
Xinyuan
X
Duan
Yourong
Y
D001120:Arginine / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry*; D003500:Cyclization; D005998:Glycine / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D011091:Polyesters; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013057:Spectrum Analysis
D010455:Peptides; D011091:Polyesters; D011108:Polymers; D011107:Polylysine; D001224:Aspartic Acid; D019344:Lactic Acid; C033616:poly(lactide); D001120:Arginine; D005998:Glycine
Science. 1994 Apr 22;264(5158):569-71
7512751
Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7934-8
1518816
Bioconjug Chem. 2003 Mar-Apr;14 (2):274; author reply 275
12643734
J Clin Oncol. 1996 Feb;14(2):405-14
8636750
Bioconjug Chem. 1998 Nov-Dec;9(6):708-18
9815164
Biomacromolecules. 2007 Mar;8(3):874-84
17315946
Colloids Surf B Biointerfaces. 2007 Mar 15;55(1):59-66
17207611
Bioconjug Chem. 1997 Sep-Oct;8(5):735-42
9327139
J Med Chem. 2004 Nov 4;47(23 ):5630-40
15509162
Cancer Res. 1990 Oct 15;50(20):6757-64
2208139
Biomacromolecules. 2005 Mar-Apr;6(2):1132-9
15762686
Curr Drug Targets. 2003 Feb;4(2):123-31
12558065
Colloids Surf B Biointerfaces. 2007 Apr 1;55(2):222-8
17254755
Clin Cancer Res. 1998 Nov;4(11):2625-34
9829725
Nature. 1984 May 3-9;309(5963):30-3
6325925
Semin Oncol. 2002 Dec;29(6 Suppl 16):15-8
12516034
J Control Release. 2002 Jul 18;82(1):159-66
12106986
J Control Release. 1998 Jun;54(1):39-48
9741902
Biomacromolecules. 2005 Mar-Apr;6(2):720-5
15762635
Cancer J. 2003 May-Jun;9(3):205-13
12952305
Adv Drug Deliv Rev. 2002 Feb 21;54(2):169-90
11897144
Hematol Oncol Clin North Am. 2004 Oct;18(5):991-1006, vii
15474331
Bioconjug Chem. 2000 Sep-Oct;11(5):637-45
10995206