Sarcosine polypeptide

Fig. 7. Conversion-time curves for polymerization of NCA s (0.224 mole l l) with amines (0.015 mole l-1) at 25 C in iV.iV-dimethylformamide. O y-Ethyl-L-glutamate NCA-di-isopropylamme A y-Ethyl-L-glutamate NCA-n-hexyl-amine Q Sarcosine NCA-di-isopropylaraine Sarcosine NCA-n-hexylamine. (Reprinted from paper by C, H. Bamford, and H. Block Polyamino Acids, Polypeptides and Proteins, p, 65, Wisconsin University Press 1962 (Fig. 7)3...

Tertiary amines were amongst the first initiators of NCA polymerisation which had been described in the literature and it seems that the polymerisation of all the known NCA s may be accomplished by their action. Wessely (77) reported in 1925 that glycine and phenyl alanine NCA s are readily polymerised in pyridine at ambient temperatures, and in the following paper (72) he reported a similar polymerisation of sarcosine NCA. The polypeptides produced by this initiator apparently formed cyclic polymers since no terminal end groups could be detected 41). It is significant that appreciable quantities (a few %) ot 3-acetic-hydantoin derivatives were found in the polymers formed from glycine and phenyl alanine NCA s but none was detected in the polymerised sarcosine NCA (72). This evidence suggests that the mechanisms of polymerisation initiated by aprotic bases may be different for the non-N-substituted NCA and the N-substituded anhydrides. 

C-Alkylation of polypeptides. Seebach et al.1 report that selective C-alkylation of a sarcosine (N-methylglycine) unit in a tri- or hexapeptide with an N-protected terminal group is possible if polylithiation is eifected with excess LDA in THF with addition of LiCl (5-6 equiv.) to provide a homogeneous mixture. In some cases, addition of an aprotic dipolar solvent (DMPU) or of BuLi can improve the yield. Under these conditions, epimerization and N-alkylation are slight. The new center introduced by alkylation of Sar tends to have the (R)-configuration when the configuration at the other centers is (S). In the methylation of the tripeptide formulated in equation (I), the yield is particularly high because the Sar unit is flanked by an N-methylamino acid. In this case, aldehydes can also serve as electrophiles. Alkylation and benzylation are also possible in the presence of added DMPU. 

Despite the drawbacks of this method, it has been used to prepare a tremendous number of polypeptide hybrid block copolymers (Table 1), and when carefully executed provides reasonably well-defined samples. Synthetic polymer domains have been prepared by addition polymerization of conventional vinyl monomers, such as styrene and butadiene, as well as by ringopening polymerization in the cases of ethylene oxide and e-caprolactone. The generality of this approach allows NCA polymerization off of virtually any primary amine functionality, which was exploited in the preparation of star block copolymers by polymerization of sarcosine NCA from an amine-terminated trimethyleneimine dendritic core [37]. In most examples, the polypeptide domain was based on derivatives of either lysine or glutamate, since these form a-helical polypeptides with good solubility characteristics. These residues are also desirable since, when deprotected, they give polypep-... 

N-acyl methyltaurates, N-acyl sarcosinates, acyl isethionates, IV-acyl polypeptide condensates, polyalkoxylated ether glycolates, monoglyceride sulfates, and fatty glyceryl ether sulfonates [1,23]. 

Another type of polypeptide-containing block copolymer, amphiliphilic rod-coil diblock copolymers such as poly (/V-triflu-oroacetyl-L-lysine)-/>-sarcosine) (Kt - Sa), were also synthesized and characterized by Gallot and coworkers [47]. The hydrophobic rod block poly(A-trifluoroacetyl-L-ly-sine) (Kt) was prepared by polymerization of Kt-NCA using A-hexylamine as the initiator. After fractionation using DMF (good solvent)/water (nonsolvent), the narrowly dispersed polymer (Kt) was then used as macroinitiator to initiate polymerization of the second monomer (Sa-NCA) to afford the hydrophilic block. Final elimination of Kt and Sa homopolymers were performed by precipitation with acetone and water respectively. The synthesis of Kt-Sa diblock copolymer is shown in Scheme 3. 

Primary amine-catalyzed polymerization of NCAs in various solvents revealed that certain polar solvents themselves act as catalysts [3]. Characteristic for the catalytically active solvents is a relatively high nucleophihcity [4] (see left column in Table 15.1). This observation and the formation of cyclic polypeptides from the N-substituted sarcosine-NCA evidenced that a zwitterionic polymerization mechanism was catalyzed, which involves ROP and condensation steps (see Formula 15.2). Pyridine is known for many decades to activate carboxylic anhy-drdies by charge separation, i. e., formation of carboxylate anions plus N-acyl pyridinium ions Therefore, it is obvious that pyridine catalyzes the same zwitterionic mechanism as the nucleophilic polar solvents [5]. In the case of N-un-substitued NCAs the initiation step will be again a charge separation, but instead of... 

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