1. Cyclization enhances function of linear anti-arthritic peptides
Marina Ali, Michael Amon, Vera Bender, Andrea Bolte, Frances Separovic, Heather Benson, Nicholas Manolios Clin Immunol. 2014 Jan;150(1):121-33. doi: 10.1016/j.clim.2013.10.005. Epub 2013 Oct 12.
This study describes the biophysical and immunomodulatory features of a cyclic peptide termed C1 which consists of alternating d-, l-amino acids and is capable of inhibiting IL-2 production in vitro and reducing the induction and extent of T-cell mediated inflammation in animal models. Solid-state nuclear magnetic resonance demonstrates that the peptide orders the lipid bilayer, suggesting a transmembrane orientation, and this is supported by surface plasmon resonance indicating strong binding affinity of C1 to model membranes. In vitro cell viability and proliferation assays show that C1 does not disrupt the integrity of cell surface membranes. Permeation studies of C1 and analogs across human epidermis cells show that the stability and skin permeability are enhanced by cyclization. Treatment with C1 in an asthma and in an arthritis animal model resulted in a suppressed immune response. Cyclization may be a useful means of enhancing biological linear peptide activity and improving delivery.
2. Asymmetric Synthesis of Apratoxin E
Zhuo-Ya Mao, Chang-Mei Si, Yi-Wen Liu, Han-Qing Dong, Bang-Guo Wei, Guo-Qiang Lin J Org Chem. 2016 Oct 21;81(20):9903-9911. doi: 10.1021/acs.joc.6b02086. Epub 2016 Oct 5.
An efficient method for asymmetric synthesis of apratoxin E 2 is described in this report. The chiral lactone 8, recycled from the degradation of saponin glycosides, was utilized to prepare the non-peptide fragment 6. In addition to this "from nature to nature" strategy, olefin cross-metathesis (CM) was applied as an alternative approach for the formation of the double bond. Moreover, pentafluorophenyl diphenylphosphinate was found to be an efficient condensation reagent for the macrocyclization.
3. Improving the Fmoc Solid Phase Synthesis of the Cyclic Hexapeptide Complement C5a Antagonist, PMX205
R C Delisle Milton, S C Milton, A R Chamberlin Int J Pept Res Ther. 2011 Dec;17(4):337-342. doi: 10.1007/s10989-011-9273-9.
The anti-inflammatory drug, PMX205, is an antagonist of the C5a complement receptor and has been shown to be effective in rodent models of amyotrophic lateral sclerosis and Alzheimer's disease. This cyclic hexapeptide (c[Arg-Trp-D-Cha-Pro-Orn]-Hca) has been reported to produce relatively low yields for both the linear peptide assembly and the cyclization reaction in solution and solid phase syntheses. During attempts to reproduce the solid phase methodology, a catastrophic loss of substitution was encountered which could be avoided or reduced by the use of 2-chlorotrityl resin. Likewise, the cyclization reaction could be significantly improved by the use of FDPP (pentafluorophenyl diphenylphosphinate) at high dilution (up to 80% purified yield). Both improvements are accomplished with commercially available products.
