Oligodepsipeptides (oDPs), alternating copolymers of an alpha-amino acid and an alpha-hydroxy acid, are typically created by ring-opening polymerization (ROP) of morpholine-2,5-dione derivatives (MDs). In general, oDPs exhibit relatively high glass transition temperatures (T(g)s) caused by the strong intermolecular H-bonding between amide and ester bonds. So far, it was not reported that variation at alpha-amino acid moieties in MDs monomers lead to lower T-g. Here we explored whether the thermal properties of the oDPs can be adjusted by introducing a hexyl side chain in the alpha-hydroxy acid part of the MDs. By synthesizing a MD with an atactic pendant hexyl group at position 3, the influence of a modification at position 6 compared to a modification at position 3 towards ROP was investigated. In both cases the atactic bulky side groups hindered the H-bonding between chain segments resulting in a significant reduction of the T(g)s to a temperature around human body temperature (32 and 36 degrees C) in contrast to ROP of a MD providing a methyl group at position 3 and a T-g approximate to 65 degrees C. Such oDPs could be interesting candidate materials for biomedical applications such as degradable implants. (C) 2016 Elsevier Ltd. All rights reserved.