In our first article on peptide DEL, we introduced BioDuro's DEL platform for exploring broader peptide chemical space. The platform features a 16-billion-compound library spanning peptides 8 to 18 amino acids in length and incorporating more than 1,000 noncanonical amino acids.

But breadth is only the starting point. After peptide DEL screening, the next challenge is to evaluate enriched sequences efficiently and identify the peptide hit series worth advancing. This article follows what happens next within BioDuro's integrated peptide discovery process: how enriched sequences move into QC-informed Direct-to-Biology (D2B) approach, how hit series are prioritized, and how selected series progress through downstream synthesis toward PCC-ready candidates.

D2B scales only when synthesis and biological testing can operate at compatible throughput. BioDuro's integrated model is designed to keep the handoff from becoming the next bottleneck. Following peptide DEL selection and enrichment analysis, representative sequences are selected for off-DNA resynthesis and subsequent binding or functional testing. However, if every crude peptide sample undergoes purification before testing, the process can quickly increase turnaround time and cost as the number of sequences grows.

In BioDuro's D2B workflow, peptide designs informed by DEL enrichment analysis and virtual screening are synthesized and screened in parallel at a 96–384-well scale. Parallel cleavage and, where required, cyclization generate crude linear or cyclic peptide samples. With supporting QC data, these samples can move into binding or functional assays without further purification for every sample.

This approach enables thousands of peptides to be synthesized and evaluated in parallel. Based on BioDuro's internal analysis, D2B provides approximately 50X faster turnaround time and reduces the cost per peptide by more than 70%, with synthesis success rates of 80%–90% for linear and cyclic peptides. Assay readouts are then used to identify and prioritize hit series for confirmation and further optimization.

Speed and scale are valuable only if the resulting data can support a clear project decision. BioDuro's QC-informed D2B workflow is designed to preserve the throughput advantage of crude peptide testing while adding the sample and assay context needed for hit evaluation.

• Chemistry expands the evidence base for peptide hit evaluation: Producing related peptide designs as panels supports faster panel validation, broader SAR coverage, and an early read on practical synthesis feasibility. When connected with QC and biology data, these panels help teams assess activity across a peptide series and determine whether the series offers a practical path for further exploration before committing resources to subsequence purification.

• QC annotation provides essential context for early assay data interpretation. LC-MS confirms the presence of the intended peptide and estimates its crude purity, while a BCA-based measurement provides an approximate peptide content. Plate mapping connects these sample attributes with the corresponding assay readout. Together, these data show whether sample-related uncertainty may limit interpretation, helping teams decide which results can support initial SAR analysis and which require additional confirmation.

• Biology brings the evidence together in a decision package. Crude peptide samples are evaluated in target-appropriate binding or functional assays, with controls and reference compounds used to establish assay performance. Rather than interpreting each peptide's activity from a single assay value, the team considers each readout alongside QC status, control performance, and emerging SAR across related designs. This integrated view identifies peptide series that warrant confirmation with purified peptide material and progression into the next round of design and optimization.

With DEL, QC, biology, and peptide synthesis connected, project teams receive a single evidence package rather than separate outputs to reconcile across multiple steps. This makes it easier to identify which peptide series have sufficient support for purified confirmation and follow-up chemistry, while flagging results that require further investigation. The goal is not simply to move peptides into biology faster, but to move the right peptide series forward with enough evidence to justify the next investment.

D2B is not about choosing a single winning peptide. Its value lies in identifying hit series that warrant deeper investment. Moving those series forward may require linear, cyclic, macrocyclic, or conjugated formats, as well as noncanonical amino acids and other demanding chemistries. Drawing on extensive peptide chemistry experience, BioDuro provides the solution from hit evaluation into the synthesis work required to generate PCC-ready peptide candidates.

Peptide DEL opens the search space, D2B brings the most promising hit series into focus, and downstream synthesis moves them toward PCC-ready candidates. If you are planning or advancing a peptide discovery program, contact our team to discuss how BioDuro can support your program.