Synthesis and characterization of polyamides containing unnatural amino acids

Abstract

We describe the synthesis of several polyamides that retain the secondary structure of proteins and contain derivatizable side chains. The derivatizable side chain allows for further reaction of the polymer chain (e.g., chain cross-linking or addition of pendant groups). Polymers of alpha-amino acids containing a terminal unsaturated bond on the side chain have been synthesized. Poly-L-pentenyl glycine, poly-L-propargyl glycine, and poly-L-allyl glycine were synthesized chemically via Leuchs' anhydrides and enzymatically using subtilisin Carlsberg. Poly-L-propargyl glycine and poly-D,L-allyl glycine folded into the beta-sheet configuration whereas poly-L-pentenyl glycine assumed a helical conformation. The secondary structure of poly-L-allyl glycine and poly-D,L-pentenylglycine could not be determined conclusively. Comparison of properties between the polymers obtained chemically and enzymatically is provided.

Fibrillar gels via the self-assembly of poly(l-glutamate)-based statistical copolymers

“…Former studies have demonstrated that in statistical copolymers of BLG and L/DL-AG, the AG units acted as defects and that the overall secondary structure of the statistical copolymer was driven by that of the BLG units (in the majority), i.e., α-helical; 55 this, despite the fact that P(DLAG) homo-or block co-polymers are known to form β-sheets. 22,59 The driving force of BLG for the α-helical conformation was also demonstrated in other statistical copolymers of similar BLG to co-monomer (e.g., propargylglycine) ratios. 54 For these reasons, we concluded that AG units behave as 'defects', thereby disrupting the formation of a BLG-driven homogeneous α-helical copolymer.…”

“…None of our statistical copolymers (Table 1) gelled in toluene at room temperature even for concentrations as high as 50 g L −1 (i.e., 5% w/ v). Interestingly, after maintaining the temperature of the solutions at −35°C for only a few minutes, we observed reversible physical gelation for all P(BLG x -co-AG 1−x ) n -toluene systems (10 to 50 g L −1 ), with exception of P(BLG 0.76 -co-DLAG 0.24 ) 59 .…”

“…These observations are in agreement with CD spectroscopy studies formerly undertaken by our group on similar systems. 41 In addition, P(BLG 0.76 -co-DLAG 0.24 ) 59 , whose secondary structure exhibited the largest random coil contribution amongst all of our copolymers, did not gel in toluene at any of the investigated temperatures. This suggests that large DLAG to …”

“…To our surprise, UV-crosslinking of P(BLG 0.76 -co-DLAG 0.24 ) 59 toluene (which does not physically gel) at −77°C led to a gel. Similarly, UV-crosslinking of P(BLG x -co-AG 1−x ) n -toluene systems at room temperature also led to gels.…”

Enzyme‐Catalyzed Synthesis of Polyamides and Polypeptides

“…Poly -l -pentenyl glycine, poly -l -propargyl glycine, and poly -l -allyl glycine were synthesized chemically and enzymatically using subtilisin Carlsberg. Whereas higher molecular weights (DP = 40 -160) were achieved with chemical means, the protease -catalyzed polymers have DP = 8 -12 [37] . In a separate work involving the non -natural amino acid allyglycine ( Ag ), subtilisin Carlsberg was used to synthesize the tetrapeptide ester l -Ag -l -Phe -l -Phe -LAg -OEt in several miscible aqueous/organic solvent systems.…”