Corrigendum to “Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPα)” [Biochem. Biophys. Res. Commun. 346 (2006) 436–446]

Gilmore, Brendan; Lynas, John F.; Scott, Christopher J.; McGoohan, Caroline; Martin, Lorraine; Walker, Brian

doi:10.1016/j.bbrc.2008.08.086

Cited by 1 publication

(1 citation statement)

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“…Several dipeptides containing phosphoproline at the C ‐terminus (Xaa‐Pro P ) have been shown to act as potent inhibitors of different proteases. Among the enzymes targeted are several serine proteases that cleave the peptide bond following the proline residue in natural peptides, such as prolyl oligopeptidase (POP),4 seprase,5 and dipeptidyl peptidases of types II (DPP‐II),6,7 IV (DPP‐IV),5–8 and 8 (DPP8) 7. It has been proposed that the hydroxymethyl side chain of the serine residue in the active site attacks the phosphonate moiety, thus undergoing phosphonylation leading to irreversible enzyme inactivation.…”

Section: Introductionmentioning

confidence: 99%

Circular Dichroism and Conformational Dynamics of Cephams and Their Carba and Oxa Analogues

Frelek

Kowalska

Masnyk

et al. 2007

Chemistry A European J

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The biological activity of bicyclic beta-lactam antibiotics depends strongly on the absolute configuration of the bridgehead carbon atom. Frelek and co-workers proposed an empirical helicity rule relating the configuration of the bridgehead carbon atom to the sign of the 220 nm band in the electronic circular dichroism (CD) spectrum of beta-lactams. Here we use synthetic organic chemistry, CD spectroscopy, and time-dependent density functional theory (TDDFT) to investigate the validity of this structure-property relationship for eight model compounds. For conformationally flexible beta-lactams, substantial thermal effects are found which must be included in calculations. To this end, we combine TDDFT calculations of CD with full quantum-mechanical Born-Oppenheimer molecular dynamics (MD) simulations for the first time. The CD spectra are sampled with ground-state density functional trajectories of up to 60 ps. The MD simulations show a surprisingly high sensitivity of the CD to the molecular conformation. On the other hand, the relation between CD and thermally averaged structural parameters is much less complex. While the helicity rule does not seem to hold for individual conformers, it is confirmed by the calculations for seven out of eight systems studied if thermally averaged CD spectra and structures are considered. Since thermal effects on CD can be larger than typical inherent inaccuracies of TDDFT, our results emphasize the need for a systematic treatment of conformational dynamics in CD calculations even for moderately flexible systems. Temperature-dependent CD measurements are very useful for this purpose. Our results also suggest that CD spectroscopy may be used as a sensitive probe of conformational dynamics if combined with electronic structure calculations.

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