Synthesis and enzymatic hydrolysis of polydepsipeptides with functionalized pendant groups

Abstract

Water-soluble polydepsipeptides with functionalized side-chain groups, i. e., alternating copolymers, consisting of glycolic acid (Glc) and L-lysine (L-LYS), L-aspartic acid (LAsp) or L-glutamic acid (L-Gh) residues as a-hydroxy acid and a-amino acid residues, respectively, were synthesized, and their biodegradation behavior was investigated. Three kinds of polydepsipeptides, poly(G1c-alt-Lys), poly(G1c-alt-Asp) and poly(Glc-altGlu), were synthesized by means of ring-opening polymerization of the corresponding cyclodepsipeptides and subsequent deprotection of benzyl and benzyloxycarbonyl groups. In order to estimate the main-chain cleavage behavior of polydepsipeptides with functionalized side-chain groups, the hydrolysis behavior of the obtained water-soluble polydepsipeptides was first investigated in phosphate buffer solution with or without an enzyme in vitro.

Degradable Poly(ester amide)s for Biomedical Applications

“…Functionalized PEAs can be obtained by ring opening polymerization of morpholine-2,5-diones derived from -amino acids like L-aspartic acid, L-glutamic acid, L-lysine, L-serine (or L-tyrosine) and L-cysteine (Figure 8), which provide pendant carboxylic acid, amine, hydroxyl and thiol groups, respectively [38][39][40][41][42][43]. The synthesis of the six-membered ring required a previous protection of functional groups, which should be stable under the polymerization conditions [8].…”

“…Polydepsipeptides derived from morpholine-2,5-diones containing glycolic acid and protected L-lysine, L-aspartic acid or L-glutamic acid [40,43] have been successfully synthesized although final molecular weights were low. In general, substituted morpholine-2,5-diones have a low reactivity and strategies based on the copolymerization with more reactive lactones (e.g., -caprolactone and D,L-lactide) were proposed [14,44] as well as the copolymerization of lactones with amino acid carboxyanhydrides [45].…”

“…Biodegradable copolymers having pendant reactive groups were obtained by ring-opening polymerization of L-lactide with morpholine-2,5-diones constituted by glycolic acid and aspartic acid or L-lysine, or L-lactic acid and L-lysine [39,40]. Interestingly, these polymers showed a faster enzymatic and hydrolytic degradation than polylactide Gonsalves et al…”

Novel PLGGE graft polymeric micelles for doxorubicin delivery

“…The synthesis of (3s)-3-benzoxylcarbonylethyl-morpholine-2,5-dione (BEMD) was performed by the reaction steps as described in the literature [19]. The poly[LA-co-(Glc-altGlu(Bz)), 92:8] (PLGBG) was synthesized by ring-opening copolymerization of both BEMD (100 mg, 0.361 mmol) and LLA (598 mg, 4.151 mmol) using SnOct 2 as catalyst, i.e.…”

“…However, the application of the PLA is limited due to the high crystallinity, and the acidic degradation product of PLA would cause acute inflammation. Morpholine-2,5-dione derivative and its copolymers were good drug carriers with biocompatibility, biodegradability, non-acid degradation products and no crystallinity [18][19][20]. Copolymers of L-lactide and morpholine-2,5-dione derivative combined the properties of both PLLA and poly [morpholine-2,5-dione] [19,21].…”