Change of Direction Proves Decisive!

BY: .

Dr Sinenhlanhla Mthembu’s transition from Microbiology and Biochemistry to Pharmaceutical Chemistry during her study journey was a challenging yet rewarding experience. 

Mthembu’s master’s research introduced her to the fascinating world of peptides, particularly cysteine-containing peptides and achieving her MSc summa cum laude provided the affirmation she needed to pursue a doctoral degree in the field. 

Under the supervision of Professor Beatriz G de La Torre and co-supervision of Professor Fernando Albericio, she embarked on a PhD research venture aimed at improving the efficiency of solid-phase peptide synthesis (SPPS), particularly for cysteine-containing peptides. 

Cysteine is a crucial amino acid in pharmaceuticals, cosmetics, and nutrition, but its highly reactive thiol (-SH) group often leads to unwanted side reactions during peptide synthesis. Mthembu’s research focused on optimising SPPS to enhance the purity and yield of cysteine-containing peptides. 

Growing up in Manaba, Mthembu’s access to quality education was limited. She attended Manaba Primary School before progressing to Injula Combined School in Jozini, in the uMkhanyakude district, northern KwaZulu-Natal. Science and mathematics tuition were not always available so learners had to travel to other schools for lessons. 

Despite these obstacles, her passion for science flourished. Her undergraduate studies in Microbiology and Biochemistry ignited a deep curiosity about microbes and their roles in food, water and disease. Participation in programmes such as the Mycobacterial Genetics Course - where she isolated bacteriophages - further cemented her dedication to scientific research. 

Key findings from her PhD include: 

- Optimising Fmoc removal to minimise by-products and increasing final product yield and purity.
- Introducing morpholine as a greener and more effective alternative to piperidine, improving sustainability in peptide synthesis.
- Developing a novel two-step cleavage method to prevent S-tButylation, enhancing cysteine purity.
- Synthesising and evaluating new disulfide-reducing agents (DPDT and DMPDT) that offer milder, more selective reduction conditions.

Her innovative work has been widely recognised, with one of her PhD publications garnering over 100 citations in ChemBioChem (2020), a testament to the impact of her contributions on both academic and industrial applications. 

Mthembu is currently a postdoctoral fellow in Pharmaceutical Chemistry at the UKZN Peptide Science Laboratory in the College of Health Sciences. Her PhD work has provided her with invaluable industry exposure - her research was conducted in collaboration with Bachem, Switzerland, the largest peptide contract manufacturing research organisation in the world. She regularly engaged with Bachem’s vice-president of research, presenting findings and discussing innovative solutions. 

Her postdoctoral projects continue to involve high-profile collaborations with industry giants such as PolyPeptide Group AG, Aspen Holdings and L’Oréal, reinforcing her commitment to bridging academia with real-world pharmaceutical applications. 

Driven by a vision of innovation and inclusivity in science, Mthembu plans to expand her research expertise internationally and to spend the next two years abroad furthering her work in peptide chemistry and medicinal chemical biology. Her long-term goal is to contribute to new technologies and solutions that will drive sustainable peptide synthesis and shape modern medicine. 

Beyond her laboratory work, Mthembu is deeply passionate about mentorship and career guidance. She assists peers with CV and cover letter preparation, helping them navigate their professional journeys with confidence. Committed to inspiring the next generation, she plans to revisit schools in her hometown to introduce students to career opportunities in Science and Engineering. 

Describing herself as a ‘shy introvert’, she finds solace in writing poetry and short stories, using them as a medium to express her thoughts and emotions. Singing, though not her forte, remains a therapeutic outlet for her. 

De La Torre and Albericio congratulated Mthembu: ‘As supervisors, we are very proud of Sne’s growth during her PhD, not only as a scientist, but also as a human being. Congratulations!’

Words: MaryAnn Francis

Photograph: Sethu Dlamini