2654-97-9Relevant academic research and scientific papers
Length-Dependent Formation of Transmembrane Pores by 310-Helical α-Aminoisobutyric Acid Foldamers
Jones, Jennifer E.,Diemer, Vincent,Adam, Catherine,Raftery, James,Ruscoe, Rebecca E.,Sengel, Jason T.,Wallace, Mark I.,Bader, Antoine,Cockroft, Scott L.,Clayden, Jonathan,Webb, Simon J.
, p. 688 - 695 (2016)
The synthetic biology toolbox lacks extendable and conformationally controllable yet easy-to-synthesize building blocks that are long enough to span membranes. To meet this need, an iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini. This library was used to probe the inter-relationship of foldamer length, self-association strength, and ionophoric ability, which is poorly understood. Although foldamer self-association in nonpolar chloroform increased with length, with a ～14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 ～70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used (～2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self-association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores. This pore-forming behavior is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.
Mechanism-specified 5-exo termini differentiation of a C32-desmethyl C28-C34 aplyronine A analog segment
Bobinski, Thomas P.,Fuchs, Philip L.
, p. 3868 - 3871 (2015)
A new mild, high yielding oxidative cleavage method allows access to a critical lactone aplyronine A analog precursor. Enhanced termini selectivity is achieved, granting access to a previously unavailable C28-C34 C-32-desmethyl actin binding tail fragment
Introducing the Chiral Constrained α-Trifluoromethylalanine in Aib Foldamers to Control, Quantify and Assign the Helical Screw-Sense**
Bodero, Lizeth,Brigaud, Thierry,Chaume, Grégory,Guitot, Karine,Lensen, Nathalie,Lequin, Olivier,Ongeri, Sandrine
supporting information, (2022/01/08)
Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that adopt 310 helical structures with equal population of left- and right-handed conformers. The screw-sense preference of the helical chain may be controlled by a single chiral re
Exploration of cathepsin S inhibitors characterized by a triazole P1-P2 amide replacement
Moss, Neil,Xiong, Zhaoming,Burke, Mike,Cogan, Derek,Gao, Donghong A.,Haverty, Kathleen,Heim-Riether, Alexander,Hickey, Eugene R.,Nagaraja, Raj,Netherton, Matthew,O'Shea, Kathy,Ramsden, Philip,Schwartz, Racheline,Shih, Daw-Tsun,Ward, Yancey,Young, Erick,Zhang, Qing
, p. 7189 - 7193 (2013/01/15)
This paper details exploration of a class of triazole-based cathepsin S inhibitors originally reported by Ellman and co-workers. SAR studies involving modifications across the whole inhibitor provide a perspective on the strengths and weaknesses of this class of inhibitors. In addition, we put the unique characteristics of this class of compounds into perspective with other classes of cathepsin S inhibitors.
Improved solid-phase peptide synthesis method utilizing alpha-azide-protected amino acids.
Lundquist 4th.,Pelletier
, p. 781 - 783 (2007/10/03)
[structure: see text]. Pure alpha-azido acids were prepared using an efficient diazo transfer method followed by buffered workup. These building blocks were used to prepare small peptides on Wang resin by two approaches. Peptides prone to diketopiperazine formation were prepared in good yields by coupling acids to resin bound iminophosphoranes during Fmoc-Wang synthesis. The iminophosphoranes can also be hydrolyzed under neutral conditions to provide unprotected amines ready for further coupling.
Azido acids in a novel method of solid-phase peptide synthesis
Meldal, Morten,Juliano, Maria A.,Jansson, Anita M.
, p. 2531 - 2534 (2007/10/03)
Azido acids were produced from α-branched acids by α-bromination with NBS followed by substitution with sodium azide and the products were used in a novel method of solid-phase synthesis. The azido acids were transformed into the highly activated acid chlorides and used synthesis of extremely hindered peptides containing up to four successive diphenyl glycine or Aib residues. By reaction of the genetically encoded amino acids with TfN3 and then SOCl2 they were transformed into α-azido acid chlorides used in solid-phase peptide synthesis without racemization.
