School of Chemistry & Physics

Dr Amit Chakraborty receives his PhD in Chemistry from UKZN’s Acting Chancellor, Professor Nana Poku.

UKZN’s Peptide Sciences Lab Attracted Doctoral Graduate

Research conducted in the field of Peptide Chemistry led to Dr Amit Chakraborty being awarded a PhD.

‘The Peptide Sciences Lab at UKZN’s Chemistry Department attracted me with its research facilities and world-renowned faculties,’ said Chakraborty. ‘Since its establishment, the lab has maintained its position as one of the top research facilities in the world in developing peptide-based sustainable and green synthesis methodologies.’

Supervised by National Research Foundation (NRF) A-rated Professor Fernando Albericio and Professor Beatriz Garcia De-La-Torre, his thesis was titled: Sec-Isoamyl Mercaptan (SIT), a Disulphide-Based Versatile Protecting Group for Cysteine Side Chain.

‘Amit’s research focused on the development of synthetic tools and methodologies for cysteine chemistry used in the peptide industry,’ said Albericio. ‘Through this work, a new disulfide-based protecting group, SIT (Sec-isoamyl Mercaptan) was developed for cysteine side chain thiol which works better than other disulfide-based protections and has been commercialised.

‘In addition, a SIT-directed method was developed for the construction of disulfide bonds which brings a new dimension towards the synthesis of multi-disulfide peptides.’

‘Peptides are smaller biomolecules with a chain of two to 50 amino acids,’ said Chakraborty. ‘There are 20 proteinogenic amino acids and among them Cysteine (Cys) is the only one to have the ability of forming disulfide bonds. Due to this ability, Cys-containing peptides possess medicinal properties. There are more than 12 Cys-containing peptides approved by the USFDA (United States Food and Drug Administration) to be used as medicinal drugs.’

Chakraborty explained that chemical synthesis of Cys-containing peptide-drugs was challenging. Owing to these challenges, the synthesis processes are often commercially unsustainable, leading to high market prices for those types of drugs.

His PhD research focused on developing synthetic tools and sustainable methods to overcome the challenges in synthesis of Cys-containing peptides.

‘I’ve developed a novel Cys-based building block (Fmoc-Cys(SIT)-OH) which is fully compatible with existing Fmoc-based peptide synthesis protocols,’ he said. ‘Fmoc-Cys(SIT)-OH has overcome all the shortcomings of similar market available Cys building blocks. Fmoc-Cys(SIT)-OH is commercialised and available with Iris Biotech GmbH, Germany. In addition, I developed novel strategies for the sustainable synthesis of disulfide-rich therapeutic peptides and aggregation-prone difficult peptides.’

Chakraborty was motivated by the unprecedented development in peptide chemistry over the past few decades. ‘In recent years, these developments have mainly focused on sustainability issues,’ he said.

‘Commercial-scale synthesis of Cys-containing peptides is plagued with many shortcomings. The development of green, sustainable synthetic tools and methodologies for Cys-peptides is the need of the hour, and there is huge scope to get established as a researcher in this field.

‘This massive opportunity motivated me to conduct research in that particular field.’

He said that the synthetic tools and methodologies he had developed were of interest to peptide-based pharmaceutical industries, especially for peptide-based drug development and manufacturing.

‘My research outputs can be considered as one of the stepping stones towards achieving the ultimate goal of developing green protocols for the chemical synthesis of peptides and related biomolecules,’ he said.

With his PhD complete, Chakraborty will be taking up a position as a postdoctoral research associate at Indiana University Bloomington in the United States in the lab of Professor Richard DiMarchi. He aspires to be both an academic and an entrepreneur, jointly founding two start-ups so far.

He thanked his mother, wife, brother and friends for their support, and his supervisors for their guidance.

Words: Sally Frost

Photograph: Sethu Dlamini