Basal-bolus insulin therapy is critical for maintaining tight glycemic control in patients with diabetes mellitus, especially for type 1. It is expected that worldwide, there will be 592 million people with some form of the disease by 2035, and about 80% of cases are expected to occur in developing countries.1 Therefore it is essential that these patients are treated adequately in order to avoid a humanitarian crisis. There have been many recent advances in the development of insulin-based therapeutics. But there are still issues with long-term thermal stability, particularly for short-acting analogues that mimic prandial levels of the endogenous hormone. Compromised formulations can lead to deleterious health outcomes for patients in poorer tropical regions, where refrigeration is not ubiquitous and the electricity supply can be unreliable.2 Hence there is a need to develop new analogues that are more thermally stable. One of the degradation products is caused by disulfide shuffling, leading to covalently bonded oligomers.3 In order to block this side reaction, a non-reducible cystine isostere can be incorporated in to the structure to replace each of the three existing disulfide bonds. Therefore this presentation will report on a robust synthesis and characterization of an insulin analogue with a cystathionine bridge, in order to develop a heat-stable therapeutic.