Poly dipeptide

There are numerous further appHcations for which maleic anhydride serves as a raw material. These appHcations prove the versatiHty of this molecule. The popular artificial sweetener aspartame [22839-47-0] is a dipeptide with one amino acid (l-aspartic acid [56-84-8]) which is produced from maleic anhydride as the starting material. Processes have been reported for production of poly(aspartic acid) [26063-13-8] (184—186) with appHcations for this biodegradable polymer aimed at detergent builders, water treatment, and poly(acryHc acid) [9003-01-4] replacement (184,187,188) (see Detergency). 

The use of backbone-modified poly (amino acids) as biomaterials was first suggested by Kohn and Langer (17) who prepared a polyester from N-protected trans-4-hydroxy-L-proline, and a poly(itiuno-carbonate) from tyrosine dipeptide as monomeric starting material (12,18). 

Several such polymers have by now been prepared and were found to possess a variety of interesting material properties. Tyrosine-derived poly(iminocarbonates) (see Sec. IV) would be a specific example. These polymers were synthesized by means of a polymerization reaction involving the two phenolic hydroxyl groups located on the side chains of a protected tyrosine dipeptide (12). 

The first chiral phases introduced for gas chromatography were either amino acid esters, dipeptide, diamide or carbonyl-bis(amino acid ester) phases [721,724,756-758]. In general, these phases exhitdted poor thermal stability and are infrequently used today. Real interest and progress in chiral separations resulted from the preparation of diamide phases grafted onto a polysiloxane backbone. These phases were thermally stable and could be used to prepare efficient open tubular columns [734,756,758-762]. These phases are prepared from commercially available poly(cyano-propylmethyldimethylsiloxanes) or poly (cyanopropylmethylphenyl-... 

In an attempt to identify new, biocompatible diphenols for the synthesis of polyiminocarbonates and polycarbonates, we considered derivatives of tyrosine dipeptide as potential monomers. Our experimental rationale was based on the assumption that a diphenol derived from natural amino acids may be less toxic than many of the industrial diphenols. After protection of the amino and carboxylic acid groups, we expected the dipeptide to be chemically equivalent to conventional diphenols. In preliminary studies (14) this hypothesis was confirmed by the successful preparation of poly(Z-Tyr-Tyr-Et iminocarbonate) from the protected tyrosine dipeptide Z-Tyr-Tyr-Et (Figure 3). Unfortunately, poly (Z-Tyr-Tyr-Et iminocarbonate) was an insoluble, nonprocessible material for which no practical applications could be identified. This result illustrated the difficulty of balancing the requirement for biocompatibility with the need to obtain a material with suitable "engineering" properties. 

Amino acids used include Gly, Ala, Phe, Leu, His, co-aminoheptanoic acid, and Ala-His dipeptide. It was found that not only single amino acids were added to the dextran, but also poly(amino acid) chains formed during the reaction. 

G. M. Barratt, C. Morin, M. Appel, and I. Seyler, Intracellular delivery of a muramyl dipeptide derivative by poly(DL-lactide) nanocapsules, in In vitro and ex vivo test systems to rationalize drug design and delivery, Paris, 1993, pp. 265-268. 

Both the size of the preceding amino acid in the dipeptide X-Pro, and that of groups in the COOR residue are able to influence (730MR547 79MI6) their conformer ratio. The conformational characteristic found for the dipeptide Gly-Pro, with the glycine amino acid bonded to a bulky residue, are close to those of poly (Gly-Pro), suggesting (77MI7) that the conformational behavior of one polymer is related to local properties of dipeptide units. 

Derrien, D., Midoux, P., Petit, C., et al. Muramyl dipeptide bound to poly-L-lysine substituted with mannose and gluconoyl residues as macrophage activators. Glycoconj. J. 6 241-255, 1989. 

Table 3 Inclusion of poly(ethylene glycol) dimethyl ethers by the dipeptide (2).

A comparison of the maps of Figs. 15 and 16 illustrates similar additional steric restrictions on a poly-L-alanine chain, as one passes from a dipeptide (Fig. 15) to helical structures (Fig. 16). Further discussion of steric effects in small polypeptide structures can be found in the recent review of Ramachandran and Sasisekharan (1968). 

Venkatachalam and Ramachandran (1967) have evaluated the various nonbonded potential functions described in Section VB, by using them to calculate nonbonded potential energy contours for the dipeptide glycyl-L-alanine and for helical poly-L-alanine. The functions considered were those of Brant and Flory (1965c), De Santis et al. (1965), Scott and... 

Finally, libraries aimed to chiral resolution of racemates will be covered here in particular, the use of chiral stationary phases (CSPs) has recently been reported for the identification of materials to be used for chiral separation of racemates by HPLC. The group of Frechet reported the selection of two macroporous poly methacrylate-supported 4-aryl-1,4-dihydropyrimidines (DHPs) as CSPs for the separation of amino acid, anti-inflammatory drugs, and DHP racemates from an 140-member discrete DHP library (214,215) as well as a deconvolutive approach for the identification of the best selector phase from a 36-member pool library of macroporous polymethacrylate-grafted amino acid anilides (216,217). Welch and co-workers (218,219) reported the selection of the best CSP for the separation of a racemic amino acid amide from a 50-member discrete dipeptide iV-3,5-dinitrobenzoyl amide hbrary and the follow-up, focused 71-member library (220). Wang and Li (221) reported the synthesis and the Circular Dichroism- (CD) based screening of a 16-member library of CSPs for the HPLC resolution of a leucine ester. Welch et al. recentiy reviewed the field of combinatorial libraries for the discovery of novel CSPs (222). Dyer et al. (223) reported an automated synthetic and screening procedure based on Differential Scanning Calorimetry (DSC) for the selection of chiral diastereomeric salts to resolve racemic mixtures by crystallization. Clark Still rejxrrted another example which is discussed in detail in Section 9.5.4. 

Earlier studies include those of Merrifield and Wooley (i27) and of Katchalski et al. (128). They prepared poly-L-histidine and its copolymers with other amino acids and showed them to be active in the hydrolysis of PNPA. Noguchi and Saito prepared poly-L-histidine, its copolymers with other amino acid residue (glutamic acid 2, aspartic acid 3, serine 4, alanine 5, cystein 6, lysine 7, e-aminocaproic acid S, and tyrosine 9), and various dipeptides containing the histidyl residue 1), (129,130). The... 

The selectivities of MIPs are in many cases comparable to those of commercially available CSPs. For example, a separation factor (a) of 17.8 was found for the separation of the two enantiomers of a dipeptide on poly(methacrylic acid-co-EDMA) imprinted with one of the enantiomers (Fig. 17.5) [43]. 

It is noteworthy that the load capacity and the resolving capability increased when the tri-functional cross-linker PETRA was used instead of EDM A [20]. The same features have been seen with polymers prepared from TRIM, another trifunc-tional cross-linker. Poly(methacrylic acid-co-TRIM) imprinted with a dipeptide was able to resolve 1 mg of the racemate with almost base-line separation (analytical column 4.6 x 250 mm) (Fig. 17.7). 

It is similar in its constitution to a dipeptide except that one acid constituent has no amino group. A compound exactly analogous to it is aceto amino acetic acid, CH3—CO—NH—CH2—COOH. Such semi-peptides result when an amino acid is treated with the acid chloride of a non-amino acid analogous to the second method of preparing poly-... 

Polymerized dipeptide surfactants, which are derived from sodium A-undecylenyl-L-valine-L-leucine (l-SUVL), sodium A-undecylenyl-L-leucine-L-valine (l-SULV), sodium A-undecylenyl-L-leucine-L-leucine (l-SULL), and sodium A-undecylenyl-L-valine-L-va-line (l-SUVV), were employed. Among these dipeptides, poly(L-SULV) showed the best enantioselectiv-ity for the separation of 1,1 -bi-2-naphthol (BN). 

Isocyanide polymerization has also been used to polymerize peptide-based monomers. Cornelissen et al. [31,32] prepared oligopeptides based on alanine and functionalized the N-terminus with an isocyanide moiety. These monomers were subsequently polymerized using a Ni catalyst into /3-helical poly isocyanopeptides with the dipeptides in the side chain. It was found that these polymers formed rigid rods, which were revealed by AFM to have extremely long persistence lengths. This rigidity was caused by the formation of /5-sheets between the alanines in the side chain. The same group... 

Fig. 19. (a) Observed 15N chemical shift diagram of poly(L-alanine) in the solid state, (b) Calculated 15N shielding diagram of A-acetyl-r.-alanine methylamide (taking hydrogen bonds with two formamide molecules), as a dipeptide model of poly(L-alanine), by means of the FPT-INDO method. 

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