a. Alteplase is formulated for IV administration at pH 7.3. Suggest TWO physicochemical factors that prevent the oral administration of biologic drugs, such as alteplase.

b. Name the THREE amino acid residues located at positions 238-240 and, hence, draw the structure of this tripeptide sequence as it would predominately exist at the administration pH.

The 527-amino acid sequence of alteplase is shown below: 1SYQVICRDEKTQMIYQQHQWLRPVLRSNRVEYCWCNSGRAQCHSVPVKS5O 51 CSEPRCFNG6TCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISY100 101 RGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCRNPDRD150 151 SKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGAS200 201 CLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRR250 251 LTWEYCDVPSCSTCELRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRS300 301 PGERFLCGGILISSCWILSAAHCFQERFPH-LTVTLGRTYRVVPGEFEO350 351 KFEVEKYIVHKEFDDDTYDNDIALLOLKSDSSRCAGESSVVRTVCLPPAD400 401 LQLPDWTECELSYGKHEALSPFYSERLKEAHVRLYPS5RCTSQHLLNRT450 451 VTDNMLCAGDTRSGGPQANLHDACQ6DSGGPLVCLNDGRMTLVGIISWGL500 501 GCGQKDVPGVYTKVTNYLDWIRDNMRP 527