A robust data analytical method to investigate sequence dependence in flow-based peptide synthesis.

Computer-assisted methods, which hold the promise to transform synthetic organic chemistry, are often limited by experimental data lacking in quality, diversity, and quantity. In solid-phase peptide synthesis (SPPS), automated flow chemistry is well-suited to deliver such data, which is key for prediction and optimization of sequence-dependent "difficult couplings", and insights obtained in flow-SPPS can be transferred to batch-SPPS. The current data analysis techniques rely on the height and the width of fluorenylmethoxycarbonyl (Fmoc) deprotection peaks and perform well under standard conditions. Yet any deviation in parameters (e.g. temperature, flow rate, resin loading) leads to incomplete capture of information and exclusion from the dataset. Here, we present a flexible and robust processing and analysis method that is based on the Gaussian shape of the deprotection peaks to overcome these challenges, which drastically increases the interpretable size of our data set. Using this straightforward method retains the full information and data quality while the generation of hazardous dimethylformamide solvent waste is reduced by 50%. Overall, this work highlights how the interplay between synthetic and computational analysis enables the collection of high-quality data even under non-ideal, non-standard conditions.

Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4.

Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the circuit. Mice with the Ascl4-induced circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain wiring in adults.