The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of peptides and peptide-related compounds, which are capable of crossing biological barriers with higher penetration efficiency comparing to their parent drugs. The HPPs are capable of being converted to parent drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs/HPCs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs/HPCs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate. Methods of solid-phase synthesis of peptide HPPs/HPCs from N-terminal to C-terminal have been also developed.本發明提供了新的多肽和多肽相關化合物的高穿透性組合物(HPC)或高穿透性前藥(HPP)的組合物，與其母藥相比，該組合物能以更高的穿透效率通過生物屏障。在通過生物屏障後，HPPs能轉變為母藥或代謝物，因此用於可用母藥或代謝物治療的症狀。此外，HPPs/HPCs可以到達母藥無法到達或實現足夠治療濃度的靶區域，因此可以實現新的治療。HPPs/HPCs可以通過不同的給藥途徑給藥於對象，例如以高濃度局部給藥至症狀作用位元點，或系統給藥至生物對象後以更高速率進入體循環。本發明還提供從N-端至C-端固相合成多肽HPPs/HPCs的方法。
