title: Synthesis of peptide-cellulose conjugate mediated by a soluble cellulose derivative having β-Ala esters.
abstract: A derivatization of cellulose was investigated for gaining up the solubility for subsequent conjugation reaction. N(β)-Boc-β-Ala, was introduced to the parent cellulose using carbonyl diimidazole. Degree of substitution towards the cellulose hydroxyls was 49%. Subsequent removal of Boc in trifluoroacetic acid (TFA) yielded β-Ala-cellulose·TFA salt. A protected hexapeptide, Boc-Ser(Bzl)-Gly-Tyr(Bzl)-Ser(Bzl)-Gly-Lys(Z) was synthesized via 9 steps of peptide elongation, and the C-end carboxyl groups of the peptide was coupled with the β-Ala-cellulose in a homogenous dimethyl sulfoxide solution, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide monohydrochloride to ensure the N(β)-selective acylation. The degree of substitution of the protected peptide towards the β-amino groups of β-Ala-cellulose (DS%(/NH(2))) was 52% for 1.0 eq.mol of the protected peptide feed, and in the presence of N-hydroxysuccinimide, DS%(/NH(2)) was increased to 61%. At 4.0 eq.mol feed, almost quantitative conjugation was observed as DS%(/NH(2))=98-99%. Deprotection of the conjugate using thioanisole-TFA resulted in complete removal of Boc, Bzl on Tyr, and Z on Lys, while a very trace amount of Bzl on Ser seemed to be left uncleaved.
authors.affiliation: Institute of High Polymer Research, Faculty of Textile Science and Technology, Shinshu University, Tokida 3-15-1, Ueda 386-8567, Japan. kohkawa@shinshu-u.ac.jp
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohkawa
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nishibayashi
authors.forename: Kesavan
authors.initials: K
authors.lastname: Devarayan
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hachisu
authors.forename: Jun
authors.initials: J
authors.lastname: Araki
mesh_terms: D000215:Acylation; D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000595:Amino Acid Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002482:Cellulose / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters; D005563:Formic Acid Esters / Q000737:chemistry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013440:Sulfides / Q000737:chemistry
chemical_list: D004952:Esters; D005563:Formic Acid Esters; D009842:Oligopeptides; D013440:Sulfides; C000345:t-butyloxycarbonyl group; D002482:Cellulose; C093850:methylphenylsulfide; D000409:Alanine