Clickable Polyprolines from Azido-proline N-Carboxyanhydride

Abstract

Polyproline is a material of great interest in biomedicine due to its helical scaffold of structural importance in collagen and mucins and its ability to gel and to change conformations in response to temperature. Appending of function-modulating chemical groups to such a material is desirable to diversify potential applications. Here, we describe the synthesis of high-molecular-weight homo, block, and statistical polymers of azide-functionalized proline. The azide groups served as moieties for highly efficient click-grafting, as stabilizers of the polyproline PPII helix, and as modulators of thermoresponsiveness. Saccharides and ethylene glycol were utilized to explore small-molecule grafting, and glutamate polymers were utilized to form polyelectrolyte bottlebrush architectures. Secondary structure effects of both the azide and click modifications, as well as lower critical solution temperature behavior, were characterized. The polyazidoprolines and click products were well tolerated by live human cells and are expected to find use in diverse biomedical applications.

Synthetic Antifreeze Glycoproteins with Potent Ice-Binding Activity

“…Distinct signatures are observed for the η → π* and π →π* transitions of PPII, disordered, sheet, or α-helical conformations. − Homopolymers of βGalNAc- or βGalαGalNAcThr have not been previously prepared; however, our previous work on αGalNAc-, αGal-, and βGal-bearing polyThr revealed that they adopt extended PPII-like conformations . We should note that it can be challenging to distinguish between true PPII and extended peptide conformations . The αGalNAc amide positive ellipticity between 190 and 200 nm overlaps with the peptide π → π* transition …”

Glycosylated Polyhydroxyproline Is a Potent Antifreeze Molecule

“… Degrees of polymerization were readily tuned by altering the monomer/initiator ratios, and amino acid compositions were tuned via the NCA feed ratios. Polymer yields were quantitative and chain lengths were determined by end-group analysis as previously described ,− or by SEC/MALS/RI. See Table for representative polymer data, and the SI for additional data and experimental methodology.…”

“… a Theoretical number-average molecular weight, M n . b Observed M n as determined by c SEC/MALS/RI in DPBS for deacetylated, free hydroxyl structures, or d SEC/MALS/RI in DMF with 0.1 M LiBr for peracetylated structures, or e 1 H NMR end-group analysis as described in prior publications. ,− f Observed degree of polymerization, DP. g Polymer dispersity, Đ , as determined by SEC/MALS/RI as described in [c] and [d] or for the sample noted with (−), the dispersity could not be determined due to poor solubility in DMF and DPBS. …”

“…NCAs were dissolved in anhydrous THF at 50 mg/mL in a vial or a bomb tube. To the NCA solution, a 30 mg/mL solution of (PMe 3 ) 4 Co or preinitiated Ni complex in THF was added. , PolyPro homopolymer was prepared using hexylamine as previously described . The NCA:initiator ratio varied, yielding different-length polypeptides.…”

“…The vials were left in the glovebox at ambient temperature, and the bomb tubes were removed from the glovebox and heated at 50 °C for 5–72 h. The reaction progress was monitored by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Upon completion, a portion of the polypeptides was removed for molecular weight analysis by size exclusion chromatography coupled to multiangle light scattering and refractive index detectors (SEC/MALS/RI) or end-capping and 1 H NMR. ,− Representative data can be found in the Supporting Information.…”