Principal Scientist / Associate Director - Peptide Medicinal Chemistry

WuXi AppTec•Natick, MA

About The Position

WuXi AppTec is seeking a highly motivated Principal Scientist / Associate Director to join its global peptide discovery team. The peptide discovery group combines mRNA Display, Phage Display, Peptide DNA-Encoded Libraries (DEL), and peptide chemistry to discover and optimize novel macrocyclic peptide therapeutics. The role leads the design and optimization of peptide and macrocyclic peptide hits and leads originating from WuXi AppTec's discovery platforms. Its primary focus is translating screening hits into optimized lead compounds through SAR exploration and rational design, advancing initial peptide hits toward compounds with improved potency and developability. The position connects peptide hit discovery with medicinal chemistry-driven lead optimization and works cross-functionally with display scientists, peptide chemists, and teams supporting biochemical, cellular, ADME, and DMPK studies. Position level will be determined by the candidate's experience, scientific leadership, and demonstrated ability to lead peptide medicinal chemistry and lead optimization programs. The successful candidate will provide scientific leadership across peptide discovery and lead optimization programs, establish medicinal chemistry strategies and priorities, guide scientists and multidisciplinary teams, and communicate program findings and recommendations to internal and external stakeholders. The job description notes that employees may also be asked to perform other job-related duties as requested by Management.

Requirements

Ph.D. in Medicinal Chemistry, Peptide Chemistry, Organic Chemistry, Chemical Biology, or a related discipline.
7+ years of relevant experience in peptide therapeutics, peptide medicinal chemistry, or drug discovery.
Demonstrated success progressing peptide or macrocyclic peptide programs through hit-to-lead and lead optimization.
Strong track record of SAR exploration and translating initial screening hits into optimized lead compounds.
Ability to independently develop and execute medicinal chemistry strategies and make data-driven optimization decisions.
Experience leading multidisciplinary drug discovery programs and working effectively across discovery functions.
Strong expertise in peptide medicinal chemistry and SAR-driven optimization.
Strong understanding of peptide and macrocycle design.
Experience with solid-phase peptide synthesis (SPPS), peptide characterization, LC-MS, and HPLC.
Understanding of peptide developability, including stability, permeability, solubility, and physicochemical properties.
Strong written and verbal communication skills, including the ability to communicate SAR, results, optimization strategies, and program recommendations clearly to multidisciplinary teams and senior scientific leadership.
Ability to work independently while collaborating effectively across discovery functions.

Nice To Haves

Postdoctoral experience in peptide drug discovery or medicinal chemistry.
Experience mentoring scientists and providing scientific direction to project teams.
Experience with noncanonical amino acids and/or chemically modified peptides.
Familiarity with structural biology and computational approaches to peptide design.
Experience in macrocyclic peptide therapeutics.
Experience with mRNA Display.
Experience with Phage Display.
Experience with Peptide DNA-Encoded Libraries (DEL).
Experience with peptide backbone modification.
Experience in structure-based peptide design.
Experience interpreting structural biology data, such as X-ray crystallography or cryo-EM, and applying structural insights to peptide design.
Experience in peptide ADME and developability optimization.
Experience with protein-protein interaction targets.
Experience with intracellular peptide therapeutics.
Experience working with internal or external peptide chemistry resources.

Responsibilities

Lead medicinal chemistry strategies for peptide and macrocyclic peptide hit-to-lead and lead optimization programs; serve as medicinal chemistry lead and provide scientific direction to multidisciplinary project teams.
Work with display and DEL teams to translate screening hits into optimized lead series through rational design, analogue synthesis, and iterative SAR development.
Develop SAR hypotheses and design analogues using sequence scanning, amino acid substitution, conformational constraint, and structure-guided approaches.
Identify binding determinants and optimize peptide sequences and chemical features to improve potency, selectivity, stability, permeability, solubility, and cellular activity.
Integrate binding, kinetic, biophysical, structural, and functional data to guide analogue design and compound prioritization.
Design peptides incorporating noncanonical amino acids and other chemical modifications to improve target engagement and developability.
Design focused follow-up libraries and analogue series to explore chemical space around validated peptide scaffolds.
Incorporate stability, permeability, physicochemical, PK/PD, and in vivo data into lead optimization and compound prioritization.
Collaborate with multidisciplinary teams to interpret enrichment and screening data, identify actionable SAR trends, and define optimization strategies.
Collaborate with peptide chemistry teams to prioritize synthesis and execute iterative optimization campaigns.
Work with structural and computational scientists to incorporate structural information and modeling into peptide design where appropriate.
Provide scientific leadership across multiple peptide discovery and lead optimization programs, setting medicinal chemistry strategies and priorities, guiding hit triage and lead prioritization, and identifying scientific risks and opportunities.
Provide scientific direction and mentorship to peptide medicinal chemistry scientists and contribute to developing medicinal chemistry capabilities within the peptide discovery organization.
Communicate SAR, experimental results, optimization strategies, and program recommendations to multidisciplinary teams, senior scientific leadership, clients, and external collaborators as appropriate.
Perform other job-related duties as requested by Management.