| Bronchioloalveolar
carcinoma (BAC) is a sub-type of adenocarcinoma
of the lung that commonly occurs in middle-age
women without a history of smoking. Patients with
BAC often present with advanced disease and treatment
options are very limited. We hypothesize that
novel peptide ligands can be identified for cell-surface
receptors specific for BAC using the methods of
‘one-bead one-peptide’ combinatorial
chemistry and ‘cell-growth-on-bead’
assay. We believe that these novel peptide ligands
potentially can be developed into effective diagnostic
and therapeutic agents for improving survival
of patients with BAC. The specific aims of this
proposal are formulated as follows: 1. To design
and synthesize one-bead one-peptide combinatorial
libraries for screening novel peptide ligands
specific for BAC cells; 2. To screen, from these
libraries, for novel peptide ligands that specifically
promote cell adhesion of BAC cells; 3. To study
the structure-activity of these novel peptide
ligands in order to identify motifs essential
for cell adhesion; 4. To modify these novel ligand
peptides to optimize their biological activity
and pharmacokinetic property; 5. To investigate
tumor specificity of these peptide ligands using
human tumor specimens; and 6. To identify cell-surface
receptors specific for interaction with the novel
peptide ligands in BAC. The knowledge gained from
this project will support development of these
novel peptide ligands into potential diagnostic
and therapeutic agents for BAC.
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