A mass spectrometric solution to the address problem of combinatorial libraries

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Materials Science

Background:

• Characterizing small peptides on solid supports is crucial for combinatorial chemistry.
• Traditional methods for analyzing peptides on beads can be complex and time-consuming.

Purpose of the Study:

• To develop a method for determining the molecular weights of femtomole quantities of small peptides directly on polystyrene beads.
• To enable the direct characterization of massive combinatorial libraries.

Main Methods:

• Utilizing imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS).
• Employing selective bond cleavage of peptides from beads using trifluoroacetic acid vapor prior to TOF-SIMS analysis.

Main Results:

• Successfully determined molecular weights of peptides in femtomole quantities attached to 30- to 60-micrometer polystyrene beads.
• Demonstrated the feasibility of analyzing large numbers of beads simultaneously.

Conclusions:

• The developed TOF-SIMS approach allows for direct and efficient molecular weight determination of peptides on beads.
• This technique is applicable for high-throughput characterization of massive combinatorial peptide libraries.