Study on the cyclization tendency of backbone cyclic tetrapeptides

The cyclization kinetics of five backbone-cyclic tetrapeptides was investig ated both experimentally and computationally. The aim was to both accuratel y measure the cyclization rates in solution and develop a method that effic iently estimates the relative cyclization tendencies computationally. Progr ession of the cyclization reaction was monitored directly, yielding the kin etics of changes in the amounts of the linear precursor and the products. T hese measurements were used to calculate the reaction rates; the results we re consistent with a first-order reaction kinetics. In order to predict the cyclization rates computationally, the conformation space of the linear pr ecursors was mapped and used to construct an approximate partition function . We assumed that the cyclization tendency was correlated with the relative probability of being found in a cyclization-prone conformation of the back bone, this probability was estimated from the partition function. The resul ts supported this assumption and demonstrated that, within reasonable accur acy, we are able to predict the relative cyclization tendencies of the pept ides measured.