title: A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.
abstract: Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.
authors.affiliation: Department of Chemistry, State University of New York at Binghamton, Binghamton, NY 13902, USA.
authors.forename: Adewale
authors.initials: A
authors.lastname: Eniade
authors.forename: Madhusudhan
authors.initials: M
authors.lastname: Purushotham
authors.forename: Robert N
authors.initials: RN
authors.lastname: Ben
authors.forename: J B
authors.initials: JB
authors.lastname: Wang
authors.forename: Kathleen
authors.initials: K
authors.lastname: Horwath
mesh_terms: D021301:Antifreeze Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification*; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry*; D003451:Cryoprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification*; D003460:Crystallization / Q000379:methods*; D005615:Freezing; D006358:Hot Temperature; D007053:Ice; D033162:Incidental Findings; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013696:Temperature; D044366:Transition Temperature
chemical_list: D021301:Antifreeze Proteins; D003451:Cryoprotective Agents; D007053:Ice; D002244:Carbon