Principal Scientist / Associate Director - Peptide Medicinal Chemistry

Location: Natick, MA, US

Employment Type: OTHER

Overview

WuXi AppTec is a leading global Contract Research, Development, and Manufacturing Organization (CRDMO) providing integrated drug discovery and development services to pharmaceutical and biotechnology companies worldwide. Our peptide discovery group combines mRNA Display, Phage Display, Peptide DNA-Encoded Libraries (DEL), and peptide chemistry to discover and optimize novel macrocyclic peptide therapeutics.

 

We are seeking a highly motivated Principal Scientist / Associate Director - Peptide Medicinal Chemistry to join our global peptide discovery team. The candidate will lead the design and optimization of peptide and macrocyclic peptide hits and leads originating from WuXi AppTecs peptide discovery platforms.

 

The primary focus of this role is to translate screening hits into optimized lead compounds through SAR exploration and rational design. The ideal candidate will have a strong track record of establishing SAR and advancing initial peptide hits into lead compounds with improved potency and developability.

 

The candidate will work cross-functionally with teams including display scientists, peptide chemists, and groups supporting biochemical, cellular, ADME, and DMPK studies to integrate screening, pharmacology, and developability data into effective optimization strategies.

 

This role will connect peptide hit discovery with medicinal chemistry-driven lead optimization, enabling rapid progression from initial hits toward lead candidates. The level of the position will be determined based on the candidates experience, scientific leadership, and demonstrated ability to lead peptide medicinal chemistry and lead optimization programs.

Responsibilities

• Lead medicinal chemistry strategies for peptide and macrocyclic peptide hit-to-lead and lead optimization programs, serving as medicinal chemistry lead and providing scientific direction to multidisciplinary project teams.
• Work closely 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 key 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 efficiently explore chemical space around validated peptide scaffolds.
• Incorporate stability, permeability, physicochemical, PK/PD, and in vivo data into lead optimization and compound prioritization.
• Work closely with multidisciplinary teams to interpret enrichment and screening data, identify actionable SAR trends, and define optimization strategies that advance peptide discovery programs.
• Collaborate with peptide chemistry teams to prioritize synthesis and rapidly 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 key scientific risks and opportunities.
• Provide scientific direction and mentorship to peptide medicinal chemistry scientists and contribute to the development of medicinal chemistry capabilities within the peptide discovery organization.
• Communicate SAR, experimental results, optimization strategies, and program recommendations to multidisciplinary project teams, senior scientific leadership, clients, and external collaborators as appropriate.

Qualifications

Education

• Ph.D. in Medicinal Chemistry, Peptide Chemistry, Organic Chemistry, Chemical Biology, or a related discipline.
• Postdoctoral experience in peptide drug discovery or medicinal chemistry is desirable.

Required Experience

• 7+ years of relevant experience in peptide therapeutics, peptide medicinal chemistry, or drug discovery.
• Demonstrated success in 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.
• Demonstrated 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.
• Experience mentoring scientists and providing scientific direction to project teams is desirable.

Technical Expertise

• 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.
• Experience with noncanonical amino acids and/or chemically modified peptides is highly desirable.
• Understanding of peptide developability, including stability, permeability, solubility, and physicochemical properties.
• Familiarity with structural biology and computational approaches to peptide design is desirable.

Preferred Experience

Experience in one or more of the following areas is particularly valuable:

• Macrocyclic peptide therapeutics
• mRNA Display
• Phage Display
• Peptide DNA-Encoded Libraries (DEL)
• Noncanonical amino acids and peptide backbone modification
• Structure-based peptide design
• Experience interpreting structural biology data (e.g., X-ray crystallography or cryo-EM) and applying structural insights to peptide design
• Peptide ADME and developability optimization
• Protein-protein interaction targets
• Intracellular peptide therapeutics
• Experience working with internal or external peptide chemistry resources

Communication & Collaboration

• Strong written and verbal communication skills.
• Ability to clearly communicate SAR, experimental results, optimization strategies, and program recommendations to multidisciplinary teams and senior scientific leadership.
• Ability to work independently while collaborating effectively across discovery functions.

 

An Equal Opportunity Employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, or protected veteran status and will not be discriminated against on the basis of disability.

 

This job description does not state or imply that the above are the only duties and responsibilities assigned to this position. Employees holding this position will be required to perform any other job-related duties as requested by Management.