English Journal

Solution phase conformation and proteolytic stability of amide-linked neuraminic Acid analogues.

Saludes JP, Gregar TQ, Monreal IA, Cook BM, Danan-Leon LM, Gervay-Hague J.Author information Department of Chemistry, , University of California Davis, One Shields Ave., Davis, CA, 95616; Department of Chemistry, Washington State University, Pullman, WA, 99164.AbstractAmide-linked homopolymers of sialic acid offer the advantages of stable secondary structure and increased bioavailability making them useful constructs for pharmaceutical design and drug delivery. Defining the structural characteristics that give rise to secondary structure in aqueous solution is challenging in homopolymeric material due to spectral overlap in NMR spectra. Having previously developed computational tools for heteroologomers with resolved spectra, we now report that application of these methods in combination with circular dichroism, NH/ND NMR exchange rates and nOe data has enabled the structural determination of a neutral, δ-amide-linked homopolymer of a sialic acid analogue called Neu2en. The results show that the inherent planarity of the pyranose ring in Neu2en brought about by the α,δ-conjugated amide bond serves as the primary driving force of the overall conformation of the homooligomer. This peptide surrogate has an excellent bioavailability profile, with half-life of ∼12 h in human blood serum, which offers a viable peptide scaffold that is resistant to proteolytic degradation. Furthermore, a proof-of-principle study illustrates that Neu2en oligomers are functionalizable with small molecule ligands using 1,3-dipolar cycloaddition chemistry. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 686-696, 2013.
Biopolymers.Biopolymers.2013 Oct;99(10):686-96. doi: 10.1002/bip.22315.
Amide-linked homopolymers of sialic acid offer the advantages of stable secondary structure and increased bioavailability making them useful constructs for pharmaceutical design and drug delivery. Defining the structural characteristics that give rise to secondary structure in aqueous solution is ch
PMID 23765412

Intertwined associations in structures of homooligomeric proteins.

Mackinnon SS, Malevanets A, Wodak SJ.Author information Molecular Structure and Function Program, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.AbstractIntertwined homo-oligomers are complexes comprising identical protein subunits, where small segments or compact protein substructures (domains) are exchanged between the subunits. Using a formal definition of intertwined homo-oligomers, we survey the Protein Data Bank for all such complexes. Results show that intertwining occurs in 13,442 (24%) of all surveyed structures. A majority (∼72%) exchanges one contiguous chain segment of varying length. Another ∼10%, exchange structural domains, and the remaining ∼20% display complex intertwining topologies. Smaller proteins are more often intertwined, and intertwining is dominant in solution homodimers. These findings and analyses of various properties of the major category of intertwined complexes, their interfaces and quaternary context, support the physiological role of intertwining in promoting homooligomer stability. Furthermore, the number of different intertwining modes observed in families of related proteins is limited, and likely specific to the protein fold. These findings yield unique insights into the role of intertwining in homomeric association.
Structure (London, England : 1993).Structure.2013 Apr 2;21(4):638-49. doi: 10.1016/j.str.2013.01.019. Epub 2013 Mar 21.
Intertwined homo-oligomers are complexes comprising identical protein subunits, where small segments or compact protein substructures (domains) are exchanged between the subunits. Using a formal definition of intertwined homo-oligomers, we survey the Protein Data Bank for all such complexes. Results
PMID 23523426

Regulatory mechanisms of acetylcholine synthesis and release by T cells.

Fujii T, Takada-Takatori Y, Kawashima K.Author information Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan. tfujii@dwc.doshisha.ac.jpAbstractAIMS: Muscarinic and nicotinic acetylcholine (ACh) receptors are expressed in immune cells. ACh synthesized by choline acetyltransferase (ChAT) and released in T cells binds to these receptors. Furthermore, we have recently demonstrated the involvement of mediatophore, a homooligomer of a 16-kDa proteolipid subunit of vacuolar H(+)-ATPase, in ACh release from T cells. In this study, we investigated the effects of phorbol 12-myristate 13-acetate (PMA), dibutyryl cAMP (dbcAMP) and FK506, an immunosuppressant calcineurin inhibitor, on lymphocytic cholinergic activity in T cells.
Life sciences.Life Sci.2012 Nov 27;91(21-22):981-5. doi: 10.1016/j.lfs.2012.04.031. Epub 2012 Apr 30.
AIMS: Muscarinic and nicotinic acetylcholine (ACh) receptors are expressed in immune cells. ACh synthesized by choline acetyltransferase (ChAT) and released in T cells binds to these receptors. Furthermore, we have recently demonstrated the involvement of mediatophore, a homooligomer of a 16-kDa pro
PMID 22569292

Japanese Journal

Self-assembly of oligo(p-phenylenevinylene)-block-poly(ethylene oxide) in polar media and solubilization of an oligo(p-phenylenevinylene) homooligomer inside the assembly