A scalable and reliable manufacturing process for nikkomycin Z HCl on a scale of 170 g has been developed and optimized. The process is characterized by a 2.3 g/L fermentation yield, 79% purification yield, and >98% relative purity of the final product. This method is suitable for further scale-up and cGMP production. The Streptomyces tendae ΔNikQ strain developed during the course of this study is superior to any previously reported strain in terms of higher yield and purity of nikkomycin Z.

A biotinylated paclitaxel derivative with an extra-long chain (LC-LC-biotin) spacer arm was synthesized using an improved synthetic reaction sequence. The biotinylated paclitaxel analogue retained excellent microtubule stabilizing activity in vitro. Furthermore, it was shown that this analogue can simultaneously engage streptavidin and the binding site on microtubules, making it suitable for localization studies or for the attachment of paclitaxel to solid substrates via a streptavidin linkage.Keywords: biotin; biotinylated; paclitaxel; taxol

•Academic partnership model for supporting and coordinating academic preclinical development.•Model for providing clinical supplies for academic clinical research.•Providing academic translational centers with access to infrastructure for developing clinical candidates.The strategic goal of academic translational research is to accelerate translational science through the improvement and development of resources for moving discoveries across translational barriers through ‘first in humans’ studies. To achieve this goal, access to drug discovery resources and preclinical IND-enabling infrastructure is crucial. One potential approach of research institutions for coordinating preclinical development, based on a model from the National Institute for Pharmaceutical Technology and Education (NIPTE), can provide academic translational and medical centers with access to a wide variety of enabling infrastructure for developing small molecule clinical candidates in an efficient, cost-effective manner.