Synbeads porous-rigid methacrylic support: application to solid phase peptide synthesis and characterization of the polymeric matrix by FTIR microspectroscopy and high resolution magic angle spinning NMR.
Porous and rigid methacrylic Synbeads were optimized and applied efficiently to the solid phase peptide synthesis with the objective of improving significantly volumetric yields (0.33 mol/L calculated on the basis of maximum chemical accessibility, i.e. the maximum number of functional groups that can be acylated by FmocCl) as compared to swelling commercial polymers (from 0.06 to 0.12 mol/L). The effects of the density of functional groups and spacer length were investigated obtaining a chemical accessibility of the functional groups up to 1 mmol/g(dry). High resolution magic angle spinning (HR-MAS) was exploited to evidence the presence of "solution-like" flexible linkers anchored on the rigid methacrylic backbone of Synbeads and to study the degree of functionalization by the Wang linker. To demonstrate the efficiency of the optimized Synbeads, the peptides Somatostatin and Terlipressin were synthesized. In the case of Somatostatin, final synthetic yields of 45 and 60% were achieved by following the HCTU/DIPEA and DIC/HOBt routes respectively, with the HPLC purity always higher than 83%. In the case of Terlipressin, the synthesis was carried out in parallel on Synbeads and also on TentaGel, ChemMatrix, and PS-DVB for comparison (DIC/HOBt route). The profiles describing the synthetic efficiency demonstrated that Synbeads leads to synthetic efficiency (86%) comparable to PS-DVB (96%) or ChemMatrix (84%). In order to gain a more precise picture of chemical and morphological features of Synbeads, their matrix was also characterized by exploiting innovative approaches based on FTIR microspectroscopy with a conventional source and with synchrotron radiation. A uniform distribution of the functional groups was evidenced through a detailed chemical mapping.
Sinigoi
Loris
L
Laboratory of Applied and Computational Biocatalysis, Dipartimento di Scienze Farmaceutiche, Università degli Studi di Trieste, Piazzale Europa, 1-34127 Trieste, Italy.
Bravin
Paola
P
Ebert
Cynthia
C
D'Amelio
Nicola
N
Vaccari
Lisa
L
Ciccarelli
Laura
L
Cantone
Sara
S
Basso
Alessandra
A
Gardossi
Lucia
L
D002851:Chromatography, High Pressure Liquid; D008236:Lypressin / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008689:Methacrylates / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry*; D013004:Somatostatin / Q000138:chemical synthesis*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D000077585:Terlipressin
D008689:Methacrylates; D011108:Polymers; D008236:Lypressin; D013004:Somatostatin; D000077585:Terlipressin