Principal Scientist, Medicinal Chemistry

PsiThera; Watertown (MA); On-site; USD 180,000 - 240,000; Full time

Job summary

PsiThera, a dynamic biotech company, seeks an accomplished medicinal chemist to advance peptide therapeutics and small molecule programs from hits to development candidates. This role blends synthetic chemistry with cutting-edge computational drug discovery to rapidly optimize molecules for clinical development, involving cross-functional collaboration across CADD, biophysics, and biology teams.

The successful candidate will lead teams, advance macrocyclic peptides, and apply in silico and

Qualifications

• Education: BS, MS or PhD in organic chemistry, medicinal chemistry or a closely related field.
• Experience: 5–10 years in biotech/pharma with a track record of advancing molecules from hit to development candidate selection.
• Proficiency in solid-phase peptide synthesis and solution-phase small molecule synthesis.
• Deep knowledge of macrocyclic peptides optimization and oral delivery considerations.
• Experience leading and mentoring teams of CRO chemists and cross-functional collaboration.

Responsibilities

• Advance peptide therapeutics and small molecule programs from screening to development candidate selection.
• Lead cross-functional collaboration with CADD, biophysics, structural biology, DMPK and biology teams.
• Apply structure-based and computational drug design to optimize peptides and small molecules; oversee synthesis.
• Manage external CRO chemist teams to ensure timely delivery of targets for testing.
• Interpret analytical data to ensure compound quality and guide project milestones.
• Stay current with literature and patent filings; lead programs from concept to development candidate nomination.

Skills

Peptide synthesis

Medicinal chemistry

Computational chemistry

Structure-based design

Leadership

SAR analysis

In silico drug discovery

Education

BS/MS/PhD in Organic or Medicinal Chemistry

Tools

Automated solid-phase peptide synthesis

Solution-phase synthesis

Machine learning tools

Spotfire

Job description

PsiThera is seeking a talented and creative medicinal chemist with a strong track record of advancing peptide therapeutics and small molecule drug discovery projects from initial hits through to development candidate selection to join our dynamic, multidisciplinary team. Our science and our team are focused on combining medicinal chemistry with our cutting-edge computational platform to rapidly identify and optimize molecules into innovative medicines for patients.
We are looking for a self-motivated individual who thrives in a fast-paced, highly collaborative environment that integrates computational and experimental data to drive our programs to the clinic.The ideal candidate will have direct experience optimizing and advancing novel peptide therapeutics into clinical development, integrating a deep knowledge of synthetic and medicinal chemistry with in silico drug discovery methods to perform multiparameter optimization, including ADME/PK considerations, and rapidly advance programs from hit identification to lead selection to development candidate nomination. A successful candidate will have a deep knowledge in design and synthesis of peptides and peptidomimetics with enhanced potency, stability, and pharmacokinetic properties, strong synthetic chemistry skills, expertise in creative and practical small molecule design, experience guiding teams of CRO chemists and excellent communication skills.
This individual will join our growing medicinal chemistry team and collaborate closely across functions including computational chemistry, biophysics, structural biology, and biology teams to provide actionable insights and strategic guidance.
Key Responsibilities

• Advance peptide therapeutics, especially macrocyclic peptides and small molecule programs from screening to development candidate selection
• Champion cross-functional collaboration, in collaboration with CADD, biophysics, structural biology, DMPK and biology design molecules to achieve program goals and meet timelines
• Implement structure-based and computational-based drug design to optimize peptide and small molecule therapeutics; Prioritize and implement synthesis.
• Manage teams of external synthetic chemists to ensure timely delivery of complex target molecules for biological testing.
• Ensure data integrity and project success by interpreting analytical results to confirm compound quality.
• Stay current with chemistry, medicinal chemistry and project-relevant literature as well as with new patent application filings.
• Lead research team or serve as medicinal chemistry lead from concept through lead optimization toward clinical development.

Qualifications

• Education: BS, MS or PhD in organic chemistry, medicinal chemistry or a closely related field
• Experience: 5-10 years of experience in the biotechnology or pharmaceutical industry, with a proven track record of advancing molecules from hit to development candidate selection.
• Demonstrated expertise in organic chemistry, including proficiencies in both automated solid-phase peptide synthesis, and solution-phase small molecule synthesis.
• Demonstrated expertise in medicinal chemistry, analyzing data, designing molecules and implementing synthesis to optimize both peptides and small molecules for oral delivery.
• Deep knowledge of macrocyclic peptides optimization, including properties required for oral administration.
• Proficient in structure-based ligand design to guide peptide and small molecule optimization.
• Experience with computational modeling and simulation for design and optimization of peptides and small molecules.
• Experience utilizing peptide informatics tools for SAR
• Familiarity with machine learning and AI-driven platforms in drug discovery.
• Experience leading and managing teams of external chemists
• Experience in a leadership role is preferred, as a project lead or co-lead, as well as functional area lead for medicinal chemistry.
• Hands-on and collaborative attitude with proven ability to work across drug discovery disciplines, including biology, structure biology, computational chemistry and biophysics.
• Excellent communication skills, with the ability to inspire, collaborate and lead in a multidisciplinary environment.
• Excellent organizational skills and attention to detail, with a strong passion for learning new concepts and technologies.

Additional Qualifications

• Familiarity with library-based screening technologies (DEL, mRNA display , phage display) and direct experience with screen follow-up and fragment-based drug discovery.
• Experience with progressing programs through lead optimization for immunology targets
• Familiarity with molecular modeling tools
• Proficiency with data analysis tools such as Spotfire

PsiThera is creating better therapeutics through an integrated molecular design paradigm that leverages best-in-class physics-based and AI technologies honed through decades of research and innovation. Our focus is first-in-class inflammation and immunology (I&I) small molecule therapeutics. We have assembled a diverse team with extensive experience across disciplines ranging from physics and computer science to chemistry, biology, biochemistry, and structural biology. This continuum of complementary skills drives our scientific vision to deliver meaningful therapeutics to patients in need. We are patient-inspired, perseverant, synergistic, supportive, intrepid, and inclusive. If you’re passionate about advancing medicine in a fast-paced, innovative environment, and eager to contribute to a team that blends advanced computation with drug discovery, PsiThera might be the perfect fit for you.
At PsiThera, we are a lean, high-performing team dedicated to pushing boundaries and achieving growth—both personally and scientifically. We seek individuals who are smart, collaborative, and thrive in a dynamic, early-stage biotech environment.
Read More About Us
Our Story: https://psithera.com/company/