title: Inulin crystal initiation via a glucose-fructose cross-link of adjacent polymer chains: atomic force microscopy and static molecular modelling.
abstract: Semi-crystalline microparticles of inulin (MPI) have clinical utility as potent human vaccine adjuvants but their relevant surface structure and crystal assembly remain undefined. We show inulin crystal surfaces to resemble multi-layered, discoid radial spherulites resulting from very rapid formation of complex tertiary structures, implying directed crystal initiation. Physical and in silico molecular modelling of unit cells confirm steric feasibility of initiation by hydrogen-bonded cross-linking of terminal glucose to a fructose of another chain, mimicking bonding in sucrose crystals. A strong, chelate-like dual H-bond is proposed to compel the known antiparallel alignment of inulin chains. Such cross-linking would require one extra fructose per chain in the native inulin crystal, as observed. Completion of five H-bonded internal ring-domains would 'lock in' each new 6-fructose structural unit of each antiparallel helix pair to create a new isoform. All known properties of inulin isoforms follow readily from these concepts.
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, SA, Australia 5042; Cancer Research Laboratory, Australian National University Medical School at The Canberra Hospital, Garran, ACT, Australia 2605; John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia 2601. Electronic address: peter.cooper@anu.edu.au.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Cooper
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, SA, Australia 5042.
authors.forename: K Harinda
authors.initials: KH
authors.lastname: Rajapaksha
authors.affiliation: Mawson Institute, University of South Australia, Mawson Lakes, SA, Australia 5095.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Barclay
authors.affiliation: Mawson Institute, University of South Australia, Mawson Lakes, SA, Australia 5095.
authors.forename: Milena
authors.initials: M
authors.lastname: Ginic-Markovic
authors.affiliation: Mawson Institute, University of South Australia, Mawson Lakes, SA, Australia 5095.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Gerson
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, SA, Australia 5042; Department of Endocrinology, Flinders Medical Centre/Flinders University, Bedford Park, SA, Australia, 5042. Electronic address: nikolai.petrovsky@flinders.edu.au.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
mesh_terms: D002236:Carbohydrate Conformation; D005632:Fructose / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D007444:Inulin / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008863:Microspheres; D008958:Models, Molecular
chemical_list: D005632:Fructose; D007444:Inulin; D005947:Glucose
keywords: Adjuvant; Fructose (PubChem CID: 5984); Glucose (PubChem CID: 5793); Glycerol (PubChem CID: 753); Inulin from chicory (PubChem CID: 16219508); Isoform; Model; Structure; Sucrose (PubChem CID: 5988); Vaccine; l-Xylose (PubChem CID: 95259)